IndraLab

Statements



sparser
"Based on these data, we wondered whether such up-regulation of USP2-AS1 had some association with the malignant behaviors of ovarian cancer cells."

sparser
"Therefore, loss-of-function assays were designed via transfecting sh-USP2-AS1#1 or sh-USP2-AS1#2 into A2780 and SKOV3 cells to effectively induce USP2-AS1 silence ( xref )."

sparser
"Then EdU assay, TUNEL assay, JC-1 assay, and transwell assay were conducted to observe the effect of USP2-AS1 knockdown on cell biological behaviors."

sparser
"The results of EdU assay demonstrated that USP2-AS1 depletion obviously suppressed ovarian cancer cell proliferation ( xref )."

sparser
"However, the outcomes of TUNEL assay and JC-1 assay indicated that cell apoptosis was remarkably strengthened due to USP2-AS1 knockdown ( xref and xref )."

sparser
"Moreover, transwell assay results revealed that USP2-AS1 deficiency seriously hampered the migration of ovarian cancer cells ( xref )."

sparser
"Collectively, USP2-AS1 is up-regulated in ovarian cancer tissues and cells and its down-regulation is effective to depress the malignant phenotypes of ovarian cancer cells."

sparser
"USP2-AS1 is Capable of Binding with miR-520d-3p."

sparser
"Therefore, we aimed to study the in-depth mechanism of USP2-AS1 in ovarian cancer."

sparser
"First, FISH assay and subcellular fractionation assay assisted us to analyze the location of USP2-AS1, and the results indicated the existence of most USP2-AS1 in the cytoplasm of A2780 and SKOV3 cells ( xref and xref )."

sparser
"Further, miR-520d-3p was shared by the prediction of both ENCORI () and ReGRNA () to have the possibility to interact with USP2-AS1 ( xref )."

sparser
"Furthermore, RIP assay demonstrated that USP2-AS1 and miR-520d-3p were significantly abundant in the anti-Ago2 group compared with the anti-IgG group ( xref ), implying the coexistence of them in RNA-induced silencing complexes (RISCs)."

sparser
"Meanwhile, we also discovered the plentiful enrichment of miR-520d-3p in the Bio-USP2-AS1 probe group in A2780 and SKOV3 cells, and the high enrichment of USP2-AS1 captured by Bio-miR-520d-3p-WT ( xref and xref )."

sparser
"Besides, we exhibited the underlying binding sites of miR-520d-3p and USP2-AS1 that were predicted via ENCORI ( xref )."

sparser
"After that, we conducted luciferase reporter assays to verify the interaction between USP2-AS1 and miR-520d-3p."

sparser
"As a result, the luciferase activity of USP2-AS1 WT was overtly declined by miR-520d-3p mimics compared with NC mimics, while that of USP2-AS1 Mut had almost no change ( xref )."

sparser
"By contrast, inhibiting miR-520d-3p led to visibly enhanced luciferase activity of USP2-AS1 WT, with no apparent alteration on that of USP2-AS1 Mut ( xref and xref )."

sparser
"To sum up, USP2-AS1 is able to function as a ceRNA via sponging miR-520d-3p."

sparser
"MiR-520d-3p Silence Abolishes the Effect of USP2-AS1 Down-Regulation on Ovarian Cancer Cell Proliferation, Apoptosis, and Migration."

sparser
"As indicated by the results of EdU assay, we observed that the EdU positive cell rate that was reduced by silenced USP2-AS1 was re-increased by miR-520d-3p inhibitor ( xref )."

sparser
"Also, the elevated apoptosis rates of A2780 and SKOV3 cells due to USP2-AS1 deficiency were reversed under miR-520d-3p inhibition ( xref and xref )."

sparser
"Furthermore, USP2-AS1 depletion resulted in suppression on ovarian cancer cell migration, which was then absolutely abolished by miR-520d-3p down-regulation ( xref )."

sparser
"Taken together, we certified that USP2-AS1 promotes cell proliferation and migration by inhibiting miR-520d-3p in ovarian cancer."

sparser
"USP2-AS1 Acts as a ceRNA to Augment KIAA1522 by Sponging miR-520d-3p."

sparser
"Importantly, it manifested that miR-520d-3p overexpression remarkably inhibited the expression of KIAA1522 ( xref ), and that KIAA1522 expression inhibited by USP2-AS1 silence was rescued by miR-520d-3p depletion ( xref )."

sparser
"Furthermore, RIP assay confirmed that USP2-AS1, miR-520d-3p, and KIAA1522 co-existed in Ago2-composed RISCs ( xref )."

sparser
"Further, we observed that the decreased KIAA1522 expression resulting from depleted USP2-AS1 was reversed by miR-520d-3p inhibitor, while such recovery was counteracted in response to the absence of KIAA1522 ( xref )."

sparser
"Collectively, all data suggested that USP2-AS1 acts as a ceRNA of KIAA1522 by competitively binding to miR-520d-3p."

sparser
"USP2-AS1 Accelerates Ovarian Cancer Development by miR-520d-3p/KIAA1522 Axis."

sparser
"The results of EdU assay showed that the suppression on ovarian cancer cell proliferation caused by the loss of USP2-AS1 was fully countervailed by miR-520d-3p reduction, while such reversion was then offset by KIAA1522 inhibition ( xref )."

sparser
"Finally, a recent study also reported that ubiquitin specific peptidase 2 antisense RNA 1 (USP2-AS1) overexpression under hypoxia diminished lenvatinib efficacy by increasing HIF-1α expression in liver cancer [ xref ]."

sparser
"Two additional loci ( MC2R and USP2-AS1 ) were significant for the top 10% survival in the analysis of parental lifespan."

sparser
"Likewise, lncRNA USP2-AS1 was demonstrated to promote the growth of HCC by stimulating YBX1-mediated HIF1α protein translation under a hypoxia environment [ xref ]."

sparser
"USP2-AS1 decreases phosphorylated YAP and increases the total level of YAP1, promoting the proliferation and metastasis of CRC cells [ xref ]."

sparser
"In this study, we confirmed USP2-AS1 binds to YBX1, but whether USP2-AS1 changed the protein levels of HIF1α by affecting the transcription or translation level of YBX1 remains unclear."

sparser
"We found a positive correlation of expression between YBX1 and USP2-AS1 in TCGA-LIHC ( xref ), so we hypothesized USP2-AS1 may increase HIF1α protein levels by affecting the expression of YBX1."

sparser
"Unfortunately, We further demonstrated that overexpression or knockdown of USP2-AS1 failed to cause significant changes in YBX1 mRNA or protein levels ( xref and xref )."

sparser
"These results suggested that USP2-AS1 did alter the protein levels of HIF1α under hypoxia, but not affected the transcriptional or translation levels of YBX1."

sparser
"USP2-AS1 Enhances YBX1 Binding to HIF1α mRNA Under Hypoxia."

sparser
"We investigated whether USP2-AS1 could enhance the effect of YBX1 on the translation of HIF1α protein by binding to YBX1."

sparser
"We observed that under hypoxic conditions, overexpression of USP2-AS1 increased the binding efficiency of YBX1 to USP2-AS1 and significantly increased the effective binding of YBX1 to HIF1α mRNA ( xref )."

sparser
"The knockdown of USP2-AS1 had the opposite effect on the binding level of YBX1 and HIF1α mRNA ( xref )."

sparser
"We used small interference RNA to change the expression of YBX1 in USP2-AS1 overexpression or knockdown cell lines ( xref )."

sparser
"The effect of overexpression or knockdown of USP2-AS1 on the translation level of HIF1α protein under hypoxia was significantly abrogated after the knockdown of YBX1 ( xref )."

sparser
"Cell proliferation, migration, and invasion experiments also showed that knockdown of YBX1 eliminated the effect of USP2-AS1 on the growth of HCC cells ( xref , xref )."

sparser
"The results suggest that USP2-AS1 can increase the protein levels of HIF1α by enhancing YBX1 protein binding to HIF1α mRNA under hypoxia, ultimately promoting the growth and development of HCC."

sparser
"USP2-AS1 Knockdown Enhances the Efficacy of Lenvatinib on HCC in Mice Tumor Xenograft Model."

sparser
"To further explore the role of USP2-AS1 acting on the growth of HCC in vivo , we constructed tumor xenograft model in mice by using USP2-AS1 overexpression or knockdown Huh7 cell line."

sparser
"The tumor xenograft model showed that overexpression of USP2-AS1 promoted the growth of tumor while USP2-AS1 knockdown inhibited the proliferation of HCC in vivo ( xref )."

sparser
"An eight-lncRNA (SLC25A30-AS1, HPN-AS1, LINC00607, USP2-AS1, HCG20, LINC00638, MKLN1-AS and LINC00652) prognostic score model was constructed for HCC, which was highly associated with TMB and immune infiltration."

sparser
"These results suggest USP2-AS1 overexpression or knockdown can affect the growth of tumor in our mice tumor xenograft model."

sparser
"Also, the outcomes of transwell assays exhibited that USP2-AS1 silence successfully inhibited ovarian cancer cell migration to a great extent, which was abolished after inhibiting miR-520d-3p; and KIAA1522 depletion further reversed above phenomenon induced by miR-520d-3p inhibition ( xref )."

sparser
"In conclusion, USP2-AS1 accelerates ovarian cancer progression by miR-520d-3p/KIAA1522 axis."

sparser
"Hypoxia-inducible factors (HIFs) are critical transcriptional activators mediating tumor hypoxia metabolism, and their imbalance plays an important role in tumor development ( xref ), so we explored whether the expression of USP2-AS1 affects the levels of HIF1α under hypoxia."

sparser
"However, the overexpression of USP2-AS1 did not affect the levels of HIF1α mRNA in Huh7 or MHCC97H cells, and the knockdown of USP2-AS1 also did not affect the HIF1α mRNA in Huh7 ( xref )."

sparser
"Interestingly, we found that overexpression of USP2-AS1 increased HIF1α protein levels under hypoxia while USP2-AS1 knockdown reduced the protein levels of HIF1α compared with the control group ( xref and xref )."

sparser
"However, no changes in HIF2α mRNA and protein levels were observed after knockdown or overexpression of USP2-AS1 (data not shown), indicating that the effect of USP2-AS1 on HIF1α protein levels is specific."

sparser
"Previous studies have confirmed that lncRNA USP2-AS1 [ xref ], HOXD-AS1 [ xref ] and HEIH [ xref ] are upregulated in OC, which can, in effect, promote the progression and development of OC cells by upregulating the expression of downstream target genes."

sparser
"In conclusion, the present study identified the expression profile of lncRNAs in the placentas of women with NDFMS and revealed for the first time, to the best of our knowledge, that lncRNA USP2-AS1 participates in the pathogenesis of NDFMS by regulating cell function."

sparser
"Some of the identified lncRNAs were highly subgroup-specific, such as lnc-CCL2-2, lnc-ABCE1-5, USP2-AS1 (GP-3-MB), and lnc-TBC1D16–3 (GP-4-MB) [ 311 ]."

sparser
"Besides, ovarian cancer tissues had more abundant USP2-AS1 expression than normal ones ( xref )."

sparser
"Moreover, USP2-AS1 was also highly expressed in ovarian cancer cell lines (ES-2, CAOV3, A2780, and SKOV3) compared to normal human ovarian surface epithelial cell line (HOSEPiC) ( xref )."

sparser
"Our results prove that USP2-AS1 is a prospective target of CRC."

sparser
"Inhibiting USP2-AS1 had anti-proliferation, pro-apoptosis, and anti-migration effects on ovarian cancer cells."

sparser
"Through the analysis of the promoter region (−3000 nt to + 174 nt) of USP2-AS1, we found 11 putative hypoxia-response elements (HRE, A/GCGTG) ( xref D)."

sparser
"Furthermore, we confirmed that USP2-AS1 sequestered miR-520d-3p to enhance KIAA1522."

sparser
"Furthermore, our results showed that USP2-AS1 could activate the PI3K/AKT signalling pathway by upregulating the expression of PHLDA2."

sparser
"In conclusion, USP2-AS1 could upregulate PHLDA2 expression by recruiting IGF2BP2 and competitively binding miR-134-5p, thus activating the PI3K/AKT signalling pathway and facilitating CRC malignant progression."

sparser
"On the other hand, the remaining 23 were considered adverse indices, including SATB2-AS1, USP2-AS1, TBX2-AS1, and others ( xref C)."

sparser
"Among these, cg16242615 (mapped to ZBTB7A) has been associated with neurodevelopmental disorders [ xref ], while cg21876869 in the intergenic region of USP2-AS1 has implications in oncogenesis [ xref ]."

sparser
"The X-tile software was employed to identify the optimal threshold value, and subsequent Kaplan-Meier analysis indicated that the genes MAPT-AS1 and USP2-AS1 possess significant prognostic relevance within both the GSE96058 dataset and the TCGA dataset ( xref )."

sparser
"To assess the combined prognostic prediction capabilities of MAPT-AS1 and USP2-AS1, the concordance index (C-index) was calculated."

sparser
"In addition, highly expressed lncRNA USP2-AS1 displays positive association with negative prognostic factors exhibited by patients with COAD."

sparser
"For example, in breast cancer, the lncRNA USP2-AS1 alleviates miRNA-mediated suppression of FDX1, promoting mitochondrial respiratory chain damage and lipoylated protein aggregation."

sparser
"In this study, we explored the expression level, roles, and mechanisms of lncRNA USP2-AS1 in CRC."

sparser
"We discovered that USP2-AS1 was overexpressed in CRC and was relevant to the poor prognosis of CRC patients."

sparser
"Functional experiments clarified that USP2-AS1 facilitated CRC cell growth and migration and reduced apoptosis."

sparser
"Animal experiments demonstrated that USP2-AS1 could promote tumor growth in vivo."

sparser
"Additionally, USP2-AS1 could absorb miR-134-5p to upregulate PHLDA2 expression."

sparser
"Mechanistically, we verified that USP2-AS1 could bind to IGF2BP2, thereby enhancing the stability of PHLDA2 mRNA."

sparser
"Foetal macrosomia is also induced by a placental increase in certain genes in mothers without GDM, such as placental expression of PPAR alpha and gamma , which are considered transcriptional regulators with key functions in lipid metabolism and miR-27b . xref On the other hand, the effects of long non-coding RNAs (lncRNA) in non-diabetic foetal macrosomia have also been studied, suggesting that the lncRNA USP2-AS1 promotes placental development by affecting the proliferative activity of placental cells. xref Moreover, another study indicated that lncRNA-SNX17 overexpression reduces the expression of miR-517a , which could play an important role in the regulation of birth weight, and increases the expression of IGF-1 in the human trophoblast cell line HTR-8/SVneo, thus enhancing the proliferation of HTR-8/SVneo. xref It also reported that lncRNA-SNX17 could promote trophoblast proliferation through the miR-517a/IGF-1 pathway and could play a role in diabetic macrosomia placentation. xref However, further studies are required to elucidate the underlying mechanisms."

sparser
"However, the role and in-depth mechanism of ubiquitin specific peptidase 2 antisense RNA 1 (USP2-AS1) in ovarian cancer have been not reported yet."

sparser
"We were absorbed into exploring the character of USP2-AS1 in ovarian cancer."

sparser
"The GEPIA database provided further evidences, and bioinformatics tools analyzed the potential molecules downstream USP2-AS1 in ovarian cancer."

sparser
"USP2-AS1 was obviously up-regulated in ovarian cancer tissues and cell lines."

sparser
"In addition, miR-520d-3p silence reversed the effect of depleted USP2-AS1 on ovarian cancer cellular behaviors, while such reversion was then abolished by KIAA1522 knockdown."

sparser
"USP2-AS1 facilitated ovarian cancer progression via miR-520d-3p/KIAA1522 axis, implying USP2-AS1 as a new perspective for the treatment of ovarian cancer."

sparser
"HOTAIR could be regarded as a potential indicator of cell cycle dysregulation in lung cancer. xref MEG3 was down-regulated in ovarian cancer cells and elicited tumor inhibitor role in this disease. xref Besides, lncRNAs have also been reported to affect tumor growth, metastasis, and drug resistance by controlling target gene expression and pathway activation. xref , xref For example, TUC338 accelerated the development of lung cancer via targeting MAPK pathway. xref CCAT1 affected breast cancer development via miR-148b. xref Unfortunately, the role and mechanism of ubiquitin specific peptidase 2 antisense RNA 1 (USP2-AS1) in ovarian cancer are still not well understood."

sparser
"In the current study, we explored the expression of USP2-AS1 in ovarian cancer tissues and cells."

sparser
"Besides, the functional analysis was used to explain the effects of USP2-AS1 interference on the biological behaviors of ovarian cancer cells."

sparser
"c-MYC promoted enhanced E2F1 expression by activating USP2-AS1, thus delaying the cellular senescence process ( xref )."

sparser
"Furthermore, we expounded the correlation among USP2-AS1, miR-520d-3p, and KIAA1522, which might help us verify USP2-AS1 as a potential therapeutic target for ovarian cancer."

sparser
"Knockdown of USP2-AS1 Represses the Progression of Ovarian Cancer."

sparser
"To expose the role of USP2-AS1 in ovarian cancer, data from GEPIA () was analyzed."

sparser
"As a result, we could observe that USP2-AS1 was significantly increased in ovarian cancer ( xref )."

sparser
"The modulation of the Hippo/YAP1 signaling pathway by the lncRNA USP2-AS1 is a crucial factor in the promotion of colon cancer progression."

sparser
"This is achieved through the interaction between USP2-AS1 and LATS1, which leads to the activation of YAP1, thereby promoting colon cancer cell proliferation, migration, and invasion [ xref ]."

sparser
"Previously, USP2-AS1 has been reported as a direct target of MYC [ xref ]."

sparser
"These results suggested that USP2-AS1 was regulated by HIF1α."

sparser
"KIAA1522 targeted by miR-125b-5p contributed to breast cancer development. xref In this research, we disclosed that USP2-AS1 accelerated ovarian cancer development by modulating miR-520d-3p/KIAA1522 axis."

sparser
"In conclusion, our findings illuminated the positive contribution of USP2-AS1 to the tumorigenesis of ovarian cancer, which was achieved via USP2-AS1/miR-520d-3p/KIAA1522 regulatory mechanism."

sparser
"In this network, USP2-AS1 acted as a ceRNA to enhance KIAA1522 expression by competitively binding with miR-520d-3p."

sparser
"Our work provided the first evidence to demonstrate USP2-AS1 as the promising therapeutic target for ovarian cancer."

sparser
"LncRNA USP2-AS1 facilitates colorectal cancer development through the PHLDA2/PI3K/AKT axis."

sparser
"LncRNA USP2-AS1 enhances cell proliferation and metastasis via downregulation of phosph-YAP in colon cancer [ xref ]."

sparser
"Regarding previously reported lncRNAs HHIP-AS1 and LOXL1-AS1 , DEA showed differential expression in SHH group as expected, while tumor suppressor lncRNA NKX2-2AS was upregulated in this group. xref LINC-NED125 , CRNDE , and OTX2-AS1 , which affect tumor progression in MB, showed differential expression patterns between groups. xref , xref , xref Additionally, CCAT1 and USP2-AS1 were found upregulated, while MIR100HG was downregulated in Gr3 MBs, consistent with prior findings. xref The expression profiles observed in our study not only confirmed the relevance of several previously characterized oncogenic and tumor-suppressive lncRNAs but also revealed novel group-specific lncRNAs which could be key molecular group biomarkers of MB."

sparser
"Additionally, various differentially expressed LncRNAs (DELncRNAs) are involved in osteogenesis, such as USP2-AS1 [ xref ], H19 [ xref ], HOTAIR [ xref ], and LINC00638 [ xref ]."

sparser
"For example, LncRNA USP2-AS1 could promote colon cancer development through Hippo/YAP1 pathway. xref SNHG17 regulated the expression of CBX3 by binding to miR-375, thus promoting the progression of colon cancer. xref LINC01578 promoted colon cancer metastasis by forming positive feedback with the NF-κB/YY1 axis. xref In this study, we found that ILF3-AS1 expression was significantly higher in COAD samples and cell lines than in the control group."

sparser
"In this study, we knocked down MYC in the HNSCC cell line FaDu and found that USP2-AS1 levels were also decreased upon MYC depletion ( xref )."

sparser
"The qRT-PCR results showed that the depletion of HIF1α remarkably inhibited the elevation of USP2-AS1 under hypoxia ( xref C)."

sparser
"By interacting with YBX1, lncRNA USP2-AS1 increases the expression level of HIF1α to decrease the therapeutic effect of lenvatinib xref ."

sparser
"G3BP1 contributes to cellular senescence by interacting with USP2-AS1 ."

sparser
"Li et al. have reported that USP2-AS1 induces the interaction between G3BP1 and the 3′-UTR of E2F1 mRNA and enhances the stability of E2F1 mRNA, a cell cycle regulator."

sparser
"These findings suggested to us that USP2-AS1 might be a direct target of HIF1α."

sparser
"Furthermore, they observed that USP2-AS1 knockdown elevated senescence-associated phenotypes and that silencing G3BP1 induced senescence in HCT116 and A549 cells ( Li et al., 2021 )."

sparser
"Thus, this study aims to reveal the role of lncRNA ubiquitin-specific peptidase 2 antisense RNA 1 (USP2-AS1) in regulating the osteogenic differentiation of HBMSCs and investigate its regulatory mechanism."

sparser
"Through bioinformatics analysis and RT-qPCR, we confirmed that USP2-AS1 expression was increased in HBMSCs after culturing in osteogenic differentiation medium (OM-HBMSCs)."

sparser
"Moreover, we uncovered that knockdown of USP2-AS1 inhibited the osteogenic differentiation of HBMSCs."

sparser
"USP2-AS1 is a poorly studied long non-coding RNA."

sparser
"Further exploration indicated that USP2-AS1 positively regulated the expression of its nearby gene USP2."

sparser
"Mechanistically, USP2-AS1 recruited lysine demethylase 3A (KDM3A) to stabilize ETS proto-oncogene 1 (ETS1), transcription factor that transcriptionally activated USP2."

sparser
"In summary, our study proved that lncRNA USP2-AS1 facilitates the osteogenic differentiation of HBMSCs by targeting KDM3A/ETS1/USP2 axis to activate the Wnt/β-catenin signalling pathway."

sparser
"Previous study has unclosed that lncRNA ubiquitin-specific peptidase 2 antisense RNA 1 (USP2-AS1) could exacerbate cell malignant behaviours in multiple cancers, including colon cancer and ovarian cancer [ xref , xref ]."

sparser
"However, whether lncRNA USP2-AS1 influences the osteogenic differentiation of HBMSCs by regulating USP2 expression remain to be further elucidated."

sparser
"In addition, patients with higher USP2-AS1 expression suffered a poorer prognosis ( xref F)."

sparser
"The current data have demonstrably proved that a majority of lncRNAs impact the development of ovarian cancer by mediating cell proliferation and apoptosis, even migration and invasion. xref , xref For example, TP73-AS1 knockdown hampered ovarian cancer cell growth by modulating cell apoptosis, and also effectively elevated the survival time of patients with this disease. xref MALAT1 stimulated epithelial ovarian cancer cell viability as well as cell migration and invasion. xref Moreover, DUXAP10 was indicated as a potential therapeutic biomarker for ovarian cancer. xref In the present work, we discovered from the GEPIA database that USP2-AS1 was highly-expressed in ovarian cancer tissues."

sparser
"Also, we unveiled the up-regulation of USP2-AS1 in ovarian cancer cells."

sparser
"Furthermore, knocking down USP2-AS1 inhibited cell proliferation and migration, but activated cell apoptosis in ovarian cancer."

sparser
"Our findings demonstrated that USP2-AS1 played as an oncogene in ovarian cancer, and targeting USP2-AS1 might be a novel manner for treating patients with this disease."

sparser
"In the present study, it was unveiled that USP2-AS1 enhanced KIAA1522 expression to aggravate ovarian cancer progression through sequestering miR-520d-3p."

sparser
"To sum up, the current study is aimed at unveiling the role of USP2-AS1 in modulating the osteogenic differentiation of HBMSCs and its correlation with its nearby gene USP2."

sparser
"USP2-AS1 promotes the osteogenic differentiation of HBMSCs."

sparser
"Therefore, other five lncRNAs, including USP2-AS1, HMMR-AS1, LINC02336, LINC01543 and NR2F1-AS1, were chosen for further analysis."

sparser
"According to RT-qPCR data, only USP2-AS1 was significantly up-regulated in OM-HBMSCs compared to PM-HBMSCs ( xref )."

sparser
"Thereafter, we chose USP2-AS1 to be our research object."

sparser
"Moreover, we applied RT-qPCR to detect the expression level of USP2-AS1 in OM-HBMSCs on day 0, 5, 10 and 15, and we found that the expression level of USP2-AS1 increased with time ( xref )."

sparser
"Subsequently, we knocked down USP2-AS1 in OM-HBMSCs with specific siRNAs and chose si1/2-USP2-AS1 for further use due to their higher knockdown efficiency (Fig. S2A)."

sparser
"Afterwards, results of ALP staining assay showed that USP2-AS1 depletion led to the significant decrease in the ALP activity of OM-HBMSCs ( xref )."

sparser
"Results of ARS staining evidenced that the absorbance value of OM-HBMSCs decreased after USP2-AS1 silence, indicating that USP2-AS1 silence inhibited the formation of mineralized bone matrix in OM-HBMSCs ( xref )."

sparser
"Subsequently, we overexpressed USP2-AS1 by transfection of pcDNA3.1-USP2-AS1 (Fig. S2B), and found that pcDNA3.1-USP2-AS1 transfection could recover the inhibited ALP activity and decreased absorbance value induced by USP2-AS1 silence (Fig. S2C-D)."

sparser
"Through RT-qPCR and western blot analyses, we found that expressions of osteogenesis-associated markers, including RUNX2, ALP, OSX and OCN were gradually increased after osteogenic induction, while USP2-AS1 depletion evidently reduced the expressions of the indicated markers (Fig. S2E-F & xref )."

sparser
"In addition, we performed subcellular fractionation and FISH assays and confirmed the distribution of USP2-AS1 in both cytoplasmic and nuclear parts of OM-HBMSCs ( xref ), which was in accordance with the predicted results on lncLocator () (Fig. S2G)."

sparser
"The above findings indicated that USP2-AS1 promotes the osteogenic differentiation of HBMSCs."

sparser
"USP2-AS1 facilitates the osteogenic differentiation of HBMSCs by up-regulating USP2."

sparser
"As some previous reports have disclosed that lncRNAs can exert their functions via regulating the adjoining genes [ xref ], we speculated that USP2-AS1 could regulate the expression of its nearby gene USP2."

sparser
"We uncovered that USP2-AS1 and USP2 were co-localized both in cell nuclei and cytoplasm ( xref , upper panel)."

sparser
"We then examined the subcellular distribution of USP2-AS1 in FaDu cells."

sparser
"Both the qRT-PCR and FISH assays revealed that USP2-AS1 was largely localized in the nuclei of the cells ( xref G,H)."

sparser
"Moreover, the genomic location of USP2-AS1 and USP2 obtained from UCSC () was shown ( xref , lower panel)."

sparser
"Then, we analysed the correlation between the expression levels of USP2-AS1 and USP2."

sparser
"As shown in xref , there existed a positive correlation between the expression levels of USP2-AS1 and USP2."

sparser
"We conducted RT-qPCR and western blot at day 14 after osteogenic induction and confirmed USP2-AS1 silencing could lead to decrease in USP2 expression in OM-HBMSCs ( xref )."

sparser
"The suppression of MYC induces cellular senescence in different types of cancer cells, including osteosarcoma and hepatocellular carcinoma. xref MYC enables cancer cells to resist senescence by being dependent on cell cycle protein-dependent kinase 2 (CDK2). xref MYC inhibits senescence by activating long noncoding RNA (lncRNA) USP2-AS1 to stabilize E2F1 mRNA. xref "

sparser
"Subsequently, results of ALP staining indicated that USP2 up-regulation could rescue the ALP activity of OM-HBMSCs impaired by USP2-AS1 silencing ( xref )."

sparser
"Thereafter, ARS staining assay verified that co-transfection of pcDNA3.1-USP2 could completely countervail the inhibitory impacts of USP2-AS1 silence on absorbance value of OM-HBMSCs ( xref )."

sparser
"As a result, co-transfection of pcDNA3.1-USP2 rescued the decreased levels of osteogenesis-associated markers caused by USP2-AS1 silencing ( xref )."

sparser
"Therefore, we confirmed that USP2-AS1 could promote the osteogenic differentiation of HBMSCs via enhancing USP2 expression."

sparser
"Case Study VI: USP2-AS1 (ENSG00000240405)."

sparser
"As we had confirmed the co-localization of USP2-AS1 and USP2 in the cytoplasm and nucleus of HBMSCs, we designed luciferase reporter assay to determine the underlying mechanism."

sparser
"From the results, we demonstrated that overexpression of USP2-AS1 could enhance the luciferase activity of pGL3-USP2 promoter rather than pmirGLO-USP2 3’UTR (Fig. S3B & xref )."

sparser
"USP2-AS1, also referred to as glycoLINC or gLINC, is an lncRNA that is known to form a scaffold to bring together several metabolic enzymes from the glycolysis pathway ( xref )."

sparser
"To conclude, USP2-AS1 promotes the osteogenic differentiation of HBMSCs by positively regulating USP2."

sparser
"We continued to investigate the transcriptional regulation of USP2-AS1 on USP2."

sparser
"These results suggested that USP2-AS1 might be a hypoxia-regulated oncogenic lncRNA during HNSCC progression."

sparser
"Related to this role, USP2-AS1 is also implicated in cancer, and its overexpression may promote cancer growth."

sparser
"USP2-AS1 up-regulates USP2 via KDM3A-mediated demethylation of H3K9me2 in ETS1 promoter."

sparser
"USP2-AS1 was observed to be a direct target of HIF1-α, and it is overexpressed in HNSCC, promoting cell proliferation and invasion through regulating DCAF13 activity ( xref )."

sparser
"Our subsequent assays were to verify whether USP2-AS1 positively regulated USP2 through modulating ETS1."

sparser
"Additionally, USP2-AS1 was observed to be upregulated in ovarian cancer ( xref )."

sparser
"First of all, we predicted the binding potential between USP2-AS1 and ETS1 on RPISeq website () ( xref )."

sparser
"Then, we conducted RIP assay and the result indicated that USP2-AS1 did not directly interact with ETS1 in OM-HBMSCs ( xref )."

sparser
"Overall, lncHUB2 was able to identify that USP2-AS1 is associated with cancer progression."

sparser
"Furthermore, ALP and ARS staining disclosed that USP2-AS1 overexpression could not rescue the inhibiting effect of ETS1 knockdown on osteogenic differentiation (Fig. S4A-B)."

sparser
"Finally, for the lncRNA USP2-AS1, lncHUB2 predicted involvement in cellular senescence and ATP production , while the role of USP2-AS1 in glycolysis was not identified."

sparser
"Continuously, we conducted RT-qPCR to unveil the impact of USP2-AS1 silencing on ETS1 expression in HBMSCs on day 14 of osteogenic induction and we noticed that ETS1 expression was reduced with USP2-AS1 silencing ( xref )."

sparser
"lncHUB2 did, however, associate USP2-AS1 with a variety of cancers."

sparser
"Furthermore, RPISeq prediction showed a high binding potential between USP2-AS1 and KDM3A ( xref )."

sparser
"Next, we determined the interaction between USP2-AS1 and KDM3A in OM-HBMSCs through RIP and RNA pull-down assays ( xref )."

sparser
"In addition, we identified that USP2-AS1 and KDM3A could not regulate each other, according to the results of RT-qPCR and western blot (Fig. S5C-D)."

sparser
"Moreover, KDM3A knockdown induced ETS1 downregulation was found to be recovered after overexpression of USP2-AS1 ( xref )."

sparser
"To conclude, USP2-AS1 up-regulates USP2 via KDM3A-mediated ETS1 upregulation."

sparser
"Finally, rescue assays revealed that overexpression of USP2 recovered the USP2-AS1 knockdown-induced downregulation of β-catenin protein (Fig. S5F)."

sparser
"Consistently, USP2 overexpression counteracted the suppressing effect of USP2-AS1 silence on the activity of Wnt/β-catenin signalling pathway (Fig. S5G)."

sparser
"Collectively, USP2-AS1 positively modulates USP2 to deubiquitinate β-catenin and induce Wnt/β-catenin pathway activation (Fig. S6)."

sparser
"Here, we selected USP2-AS1 as our research target due to its significant up-regulation in HBMSCs after osteogenic differentiation, according to the results of bioinformatics analysis and RT-qPCR."

sparser
"According to previous literatures, USP2-AS1 functions as an oncogenic factor in colon cancer and ovarian cancer [ xref , xref ]."

sparser
"The experimental results in the current study firstly verified the promoting effects of USP2-AS1 on the osteogenic differentiation of HBMSCs, which was evidenced by the results that USP2-AS1 knockdown led to the decreased ALP activity, reduced formation of mineralized bone matrix and lessened expression levels of osteogenesis-associated markers (RUNX2, ALP, OSX and OCN)."

sparser
"In this study, we found that USP2-AS1 could positively regulate the expression of its nearby gene USP2."

sparser
"Our findings demonstrated that USP2 overexpression could completely countervail the suppressing impacts of USP2-AS1 silence on the osteogenic differentiation of HBMSCs."

sparser
"Furthermore, we verified the co-localization of USP2-AS1 and USP2 in both nucleus and cytoplasm, suggesting the possibility of both transcriptional and post-transcriptional modulation mechanisms."

sparser
"However, the results of luciferase reporter assay indicated that USP2-AS1 upregulated USP2 by activating its transcription."

sparser
"USP2-AS1 upregulated EST1 expression but could not directly bind with it in OM-HBMSCs."

sparser
"Similarly, we validated that USP2-AS1 interacted with KDM3A to regulate ETS1 via the demethylation of H3K9me2, and thereby enhanced USP2 expression."

sparser
"In conclusion, our study proved that USP2-AS1 can facilitate the osteogenic differentiation of HBMSCs by recruiting KDM3A to activate USP2 transcription, and thus enhancing β-catenin protein stability to activate the Wnt/β-catenin signalling pathway."

sparser
"Results: We constructed a novel cuproptosis-related prognostic 2-lncRNAs (USP2-AS1, NIFK-AS1) signature (BCCuS) in breast cancer."

sparser
"qPCR results showed that two model lncRNAs (USP2-AS1, NIFK-AS1) and three Cuproptosis genes (FDX1, PDHA1, DLAT) expressed differently between 10 pairs of breast cancer tissue samples and adjacent samples."

sparser
"These include the following: FGD5-AS1 , FOXD2-AS1 , HNF1A-AS1 , HOXC-AS1 , HOXA11-AS , KTN1-AS1 , COX10-AS1 , MNX1-AS1 , RASAL2-AS1 , RHPN1-AS1 , SLC16A1-AS1 , USP2-AS1 , VWA8-AS1 , ZFAS1 , RGMB-AS1 , ZNF667-AS1 , and ELF3-AS1 ."

sparser
"USP2-AS1 had 11 targets and HCP5 (HLA Complex P5) had five targets (CD74, FGL2, HLA-DPA1, IFI27, NCF1)."

sparser
"The expression of CFAP43 were regulated by hsa-miR-3120-3p which may be sponged by hsa_circ_0007161, hsa_circ_0000996, hsa_circ_0069606, hsa_circ_0027707, hsa_circ_0003677, hsa_circ_0028190, hsa_circ_0052575, hsa_circ_0001513, LINC00504, USP2-AS1, LINC00535, LINC00271, AP000708.1, or DNAJC27-AS1."

sparser
"Our study shows that lncRNA USP2-AS1 is a Yes-associated protein 1 (YAP1) binding lncRNA, and inactivates Hippo signaling in COAD cells."

sparser
"Moreover, our data indicated that USP2-AS1 lowered the phosph-YAP (S127), elevated the total level of YAP1, and triggered the expression of downstream target genes in COAD cells."

sparser
"Further investigation revealed that USP2-AS1 was upregulated in HNSCC and could be used to predict poor prognosis."

sparser
"The loss- and gain-of function assays demonstrated that USP2-AS1 promotes cellular proliferation and metastasis of COAD cells."

sparser
"Clinically, the USP2-AS1 levels were significantly elevated in COAD tissues and were positively correlated with tumor grade, size, and TNM stage."

sparser
"Collectively, these findings demonstrated that USP2-AS1 modulates and regulates Hippo signaling in COAD and could be a valuable therapeutic target."

sparser
"It was reported that some lncRNAs, such as ARHGEF7-AS2, lnc-HLX-1, lnc-EXPH5-2, lnc-CH25H-2, and lnc-TDRP-3, demonstrate differential expression in these two groups, and that other lncRNAs were subgroup-specific: lnc-CCL2-2 in the WNT subgroup, lnc-ABCE1-5 in the SHH subgroup, USP2-AS1 in group 3, and lnc-TBC1D16-3 in group 4 [ xref ]."

sparser
"USP2-AS1 enhances YBX1-HIF1α mRNA binding under hypoxia, increasing HIF1α protein levels and hepatocellular carcinoma growth ( xref )."

sparser
"Through a comprehensive screening of hypoxia-regulated lncRNAs in HNSCC cells, we found that USP2-AS1 is a hypoxia-responsive lncRNA that is directly regulated by HIF1α."

sparser
"Moreover, the knockdown of DCAF13 restored the elevated cell proliferation and growth levels achieved by USP2-AS1 overexpression."

sparser
"Altogether, we found that lncRNA USP2-AS1 functions as a HIF1α-regulated oncogenic lncRNA and promotes HNSCC cell proliferation and growth by interacting and modulating the activity of DCAF13."

sparser
"In the current study, we initially screened hypoxia-regulated lncRNA in HNSCC cells by RNA-seq, before focusing on the rarely annotated lncRNA USP2 antisense RNA 1 (USP2-AS1)."

sparser
"We determined that USP2-AS1 is a direct target of HIF1α and is remarkably elevated in HNSCC compared with matched normal tissues."

sparser
"Patients with a higher level of USP2-AS1 suffered a poor prognosis."

sparser
"Next, loss- and gain-of-function assays revealed that USP2-AS1 promoted cell proliferation and invasion in vitro and in vivo."

sparser
"Mechanically, RNA pulldown and LC–MS/MS demonstrated that the E3 ligase DDB1- and CUL4-associated factor 13 (DCAF13) is one of the binding partners to USP2-AS1 in HNSCC cells."

sparser
"In addition, we assumed that USP2-AS1 regulates the activity of DCAF13 by targeting its substrate ATR."

sparser
"A biological and mechanical investigation revealed that USP2-AS1 promotes HNSCC cell proliferation and invasion by modulating DCAF13 signaling."

sparser
"USP2-AS1 Is a Hypoxia-Regulated lncRNA and Predicts Poor Prognosis in HNSCC."

sparser
"We found that USP2-AS1 was remarkably upregulated in HNSCC compared to matched normal tissues ( xref C), and more than half of HNSCC patients demonstrated a high expression of USP2-AS1 ( xref D)."

sparser
"Moreover, the combined analysis of the GTEx and TCGA-HNSCC data showed that USP2-AS1 was also significantly upregulated in HNSCC ( xref E)."

sparser
"USP2-AS1 Is Directly Regulated by HIF1α under Hypoxia."

sparser
"To investigate the molecular mechanism behind the regulation of USP2-AS1 under hypoxia, we first validated the RNA-seq results."

sparser
"As shown in xref A, the expression of USP2-AS1 was elevated by more than five-fold under hypoxia in CAL27 cells, with HIF1A-AS1, H19, LUCAT, PDK1 et al. as positive controls."

sparser
"As HIF1α is the most pivotal transcription factor under hypoxia, USP2-AS1 might be regulated by HIF1α."

sparser
"We then performed dual-luciferase reporter assays, as illustrated in xref D. The USP2-AS1 promoter reporters pHREs1+2, and especially the pHREs2 region, could be significantly responsive to hypoxia in FaDu cells ( xref D); we also noticed that pHREs1 responded moderately to hypoxia, and it seemed that HIF1α was mainly bound to the pHREs2 region."

sparser
"In contrast, increased levels of USP2-AS1 are closely linked to a poorer prognosis xref ."

sparser
"The HIF1α antibodies effectively immunoprecipitated HIF1β ( xref E) under hypoxia, and the qPCR analysis of the immunoprecipitated genomic DNA revealed that the USP2-AS1 HRE6-11 promoter region could be enriched by HIF1α antibodies ( xref F)."

sparser
"These results suggested that USP2-AS1 is directly regulated by HIF1α in HNSCC cells."

sparser
"USP2-AS1 Promotes HNSCC Progression."

sparser
"In vitro transcribed biotin-labeled USP2-AS1 and control (anti-sense of USP2-AS1) were used for RNA-pulldown experiments [ xref ] ( xref A), and we then identified the differential binding proteins by LC–MS/MS."

sparser
"The sgGSEA revealed that USP2-AS1 was positively correlated with MYC targets, glycosis, hypoxia, and glycosis signaling ( xref )."

sparser
"These findings suggested that USP2-AS1 might exert its oncogenic effects in the abovementioned aspects during HNSCC progression."

sparser
"We knocked down USP2-AS1 in FaDu cells using three shRNAs (sh#1/2/3), and qRT-PCR revealed that sh#2 was most effective ( xref A)."

sparser
"Cell proliferation analysis revealed that the silencing of USP2-AS1 inhibited FaDu cell proliferation under both normoxia and hypoxia ( xref B)."

sparser
"Cell colony formation assays in normoxia revealed that the depletion of USP2-AS1 significantly inhibited FaDu cell proliferation and growth under normoxia ( xref )."

sparser
"Cell cycle analysis found that the knockdown of USP2-AS1 resulted in cell-cycle arrest in the G0/G1 stage ( xref )."

sparser
"Moreover, subcutaneous tumor formation assays showed that the silencing of USP2-AS1 significantly inhibited tumor growth in vivo ( xref C,D)."

sparser
"To further confirm these results, we overexpressed USP2-AS1 in CAL27 ( xref E)."

sparser
"As expected, USP2-AS1 overexpression remarkably increased the proliferation and growth of CAL27 cells ( xref ), accelerated cell transitions from the G0/G1 stage to the S stage ( xref ), and enhanced tumor growth in vivo ( xref F,G)."

sparser
"Additionally, matrigel-coated trans-well assays showed that USP2-AS1 knockdown inhibited FaDu cell invasion under hypoxia ( xref ), while USP2-AS1 overexpression promoted CAL27 cell invasion ( xref )."

sparser
"In contrast, RIP assays showed that USP2-AS1 could be immunoprecipitated by Flag-DCAF13, but not 18S RNA or U1 snRNA ( xref G,H)."

sparser
"To validate the sgGSEA results, we determined the expression of cell proliferation-, death-, and glycosis-associated genes in these subcutaneous tumors and found that the knockdown of USP2-AS1 inhibited the expression of cell-cycle-progression- and glycosis-associated genes ( xref H)."

sparser
"In contrast, the overexpression of USP2-AS1 enhanced the levels of these mRNAs ( xref I)."

sparser
"All these results indicated that USP2-AS1 promotes HNSCC progression."

sparser
"USP2-AS1 Binds to DCAF13 in HNSCC Cells."

sparser
"To understand how USP2-AS1 promotes HNSCC progression, we sought to identify its binding partner in hypoxia-treated FaDu cells."

sparser
"Most of the potential binding proteins of USP2-AS1 are listed in xref B. Next, we analyzed the clinical significance of these proteins in the TCGA-HNSCC dataset and found that DCAF13 (DDB1- and CUL4-associated factor 13), a substrate receptor for the CUL4–DDB1 E3 ubiquitin–protein ligase complex [ xref ], was also highly expressed ( xref C) and positively correlated with USP2-AS1 ( xref D): a higher level of DCAF13 predicted poorer prognosis ( xref E) in HNSCC patients."

sparser
"In fact, Li et al. [ xref ] have reported that MYC stabilizes the mRNA of E2F1 by activating the lncRNA USP2-AS1, thereby increasing the level of E2F1."

sparser
"Furthermore, DCAF13 was distributed in both the nucleus and cytoplasm of FaDu cells ( xref ), similarly to USP2-AS1 ( xref H,I)."

sparser
"These findings allowed us to identity the interaction between DCAF13 and USP2-AS1."

sparser
"We then validated the binding of DCAF13 and USP2-AS1 in FaDu cells, as shown in xref F. USP2-AS1 pulled down DCAF13, but not the negative control β-actin."

sparser
"These findings demonstrated that DCAF13 binds to USP2-AS1 in HNSCC cells."

sparser
"By using the RNAfold webserver , we predicted USP2-AS1’s secondary structure and constructed two truncations (T1 and T2) ( xref I)."

sparser
"Compared to full-length USP2-AS1, both the T1 and T2 truncations, especially T2, abrogated the interaction with DCAF13 ( xref I)."

sparser
"USP2-AS1 through DCAF13 Promotes HNSCC Progression."

sparser
"Unexpectedly, tumor suppressive proteins including P53, CDKN1C, and ATR were listed ( xref A and Dataset 2); ATR was also shown to bind to USP2-AS1 according to the RNA-pulldown and LC–MS/MS data ( xref B)."

sparser
"We then assumed that USP2-AS1 might promote DCAF13 by targeting these putative tumor-suppressive substrates, especially ATR."

sparser
"And, KIAA1522 also was confirmed to be regulated by lncRNA USP2-AS1 and miR-520d-3p, and accelerated cell proliferation and migration in ovarian cancer [25] ."

sparser
"Furthermore, we also found that silencing USP2-AS1 elevated the protein level of ATR and P53 under hypoxia but not normoxia, and the results are presented in xref ."

sparser
"The overexpression of USP2-AS1 inhibited the protein levels of ATR and P53, and DCAF13 depletion restored the protein levels of ATR FaDu cells under hypoxia ( xref C)."

sparser
"We noticed that elevated levels of USP2-AS1 inhibited the accumulation of P53 under hypoxia."

sparser
"In addition, the CCK8 cell viability assays showed that the knockdown of DCAF13 restored the cell proliferation and growth by USP2-AS1 overexpression ( xref D)."

sparser
"These results demonstrated that USP2-AS1 promoted cell proliferation through DCAF13 in HNSCC."

sparser
"Herein, we reported that lncRNA USP2-AS1 is upregulated under hypoxia and is a direct target of HIF1α."

sparser
"It has been reported that some lncRNAs, such as ARHGEF7-AS2 , lnc-HLX-1 , lnc-EXPH5–2 , lnc-CH25H-2  and lnc-TDRP-3 , demonstrate differential expression in these two groups, and that other lncRNAs were subgroup-specific: lnc-CCL2–2 in the WNT subgroup, lnc-ABCE1–5 in the SHH subgroup, USP2-AS1 in group 3 and lnc-TBC1D16–3 in group 4 ( xref )."

sparser
"Both loss- and gain-of-function assays revealed that USP2-AS1 promoted cell proliferation and invasion in HNSCC."

sparser
"Moreover, patients with higher levels of USP2-AS1 were associated with undesirable clinical outcomes."

sparser
"These results suggested that USP2-AS1 exerts its oncogenic effects on HNSCC tumorigenesis and progression."

sparser
"USP2-AS1 has been reported to be possibly regulated by MYC [ xref ]."

sparser
"The regulation of USP2-AS1 by MYC and HIF1α suggests that it might take part in the crosstalk between the MYC and HIF1α signaling pathways during cancer initiation and progression."

sparser
"Herein, we demonstrated that USP2-AS1 exerts its oncogenic effect by binding to DCAF13, a substrate receptor for the CUL4–DDB1 E3 ubiquitin–protein ligase complex [ xref ]."

sparser
"In the current study, we therefore assumed that USP2-AS1 might regulate DCAF13 by targeting its substrates."

sparser
"Moreover, the overexpression of USP2-AS1 inhibited and the silencing of USP2-AS1 elevated the protein level of ATR and P53 under hypoxia in CAL27 and FaDu cells, respectively."

sparser
"All these findings suggested that USP2-AS1 might regulate DCAF13 by targeting these tumor suppressors."

sparser
"Exploring the role of USP2-AS1 in HNSCC and its clinical significance has greatly enhanced our understanding of the molecular pathology of HNSCC and provided a potential treatment target for HNSCC."

sparser
"Considering this evidence, USP2-AS1 has remarkable potential for HNSCC prognosis."

sparser
"Nevertheless, the mechanism through which USP2-AS1 affects DCAF13 by targeting its substrates should be further explored."

sparser
"Although the overexpression of USP2-AS1 has previously been associated with colorectal cancer and lung cancer progression [ xref , xref ], the current study added another level of complexity to the manner in which USP2-AS1 regulates cancer progression."

sparser
"Whether USP2-AS1 could function as an independent risk factor for HNSCC patients should be further investigated."

sparser
"A higher level of USP2-AS1 was strongly associated with the poorer overall survival of HNSCC patients in this study."

sparser
"Another intriguing example of scaffolding involves the lncRNA glycoLINC, also named USP2-AS1."

sparser
"We also found USP2-AS1 contains 6 fragments with specific secondary structures by the RNAfold Webserver ( xref )."

sparser
"This effect is further amplified by the long non-coding RNA USP2-AS1, which enhances transcriptional activation of the USP2 gene by facilitating interactions between KDM3A and ETS1 at the promoter region, thereby reinforcing β-catenin stability and promoting human bone marrow mesenchymal stem cell (HBMSC) differentiation into osteoblasts [ xref , xref , xref ]."

sparser
"In the genomic context, gLINC , also known as ubiquitin carboxyl-terminal hydrolase 2 (USP2)-antisense RNA1 (USP2-AS1) or THY1-AS1, is found on chromosome 11q23, located head to head with the USP2 gen[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Furthermore, several dysregulated lncRNAs such as LINC001152 and USP2-AS1 promote colorectal cancer cell proliferation and metastasis through overexpressing YAP1 and p-YAP1 protein levels [18,19] ."

sparser
"Notably, the expression of lncRNA USP2-AS1 is significantly upregulated in hypoxic microenvironments, activating downstream hypoxic response pathways by enhancing the interaction between the RNA-binding protein YBX1 and HIF1α mRNA, thereby stabilizing HIF1α mRNA and increasing its protein levels."

sparser
"lncRNA USP2-AS1 promotes colon cancer progression by modulating Hippo/YAP1 signaling."

sparser
"To understand the mechanism of USP2-AS1 in HCC progression under hypoxia, we performed RNA pulldown assays on Huh7 cells cultured in hypoxia for 48 hours ( xref and xref )."

sparser
"Importantly, the knockdown of USP2-AS1 markedly improved the therapeutic efficacy of the tyrosine kinase inhibitor lenvatinib and inhibited tumor growth in an in vivo model, indicating that targeting USP2-AS1 may reverse therapeutic resistance in hepatocellular carcinoma cells by disrupting HIF1α signaling ( xref )."

sparser
"Antisense lncRNA USP2-AS1 was found to promote tumor growth under hypoxia conditions; in particular, RIP and RNA pull-down assays demonstrated that USP2-AS1 can interact with YBX1 and significantly increase its binding to HIF-1α mRNA, promoting translation [ xref ]."

sparser
"Recently, Tang et al. showed that USP2-AS1 was specifically upregulated in HNC cells during hypoxia, and it was a direct transcriptional target of HIF-1α."

sparser
"Further, this hypoxia-inducible USP2-AS1 could functionally promote HNC cell growth and invasion in vitro, and tumor growth in vivo."

sparser
"It was postulated that USP2-AS1 might affect E3 ubiquitin ligase DCAF13 expression and, thus, affect the associated signaling in HNC cells [ xref ]."

sparser
"A total of 75 proteins were identified as potential molecules that may bind to USP2-AS1 by using mass spectrometry ( xref )."

sparser
"The following 29 lncRNAs were found to be associated with prognosis: AL009178.3, AC034199.1, AC017083.1, AC087588.1, AL354892.2, AC010336.7, AC125437.1, AC091153.3, AP003352.1, SCAT2, USP2-AS1, CTBP1-DT, AC016737.1, ALMS1-IT1, LINC01356, AC107032.2, AL355 SBNO1-AS1, AL024508.1 b, AC022784.6, AC008610.1, AC011298.1, AC145423.1, AC005914.1, and AC011298.1 ( xref )."

sparser
"Although these associations did not replicate in the Taiwan Maternal and Infant cohort ( n =37), other top hits did (e.g., cg21876869c in USP2-AS1 , cg00173435c in TCP11L2 , and cg18901140c in NTN1 ) ( xref )."

sparser
"The study found that an 11-lncRNA signature ( MIR100HG , lnc-CFAP100-4 , ENSG00000279542 , lnc-ABCE1-5 , USP2-AS1 , lnc-RPL124 , OTX2-AS1 , lnc-TB1D16-3 , ENSG00000230393 , ENSG00000260249 , and lnc-CCL2 ) could accurately classify MB subgroups with an average < 7% class error rate."

sparser
"Using RNA sequencing, 25 hypoxia-related lncRNAs were found to be upregulated in HCC, of which lncRNA USP2-AS1 were significantly increased under hypoxia."

sparser
"We further confirmed that USP2-AS1 was significantly upregulated in liver cancer using FISH assay and that USP2-AS1 was associated with advanced liver cancer and increased tumor size."

sparser
"Furthermore, overexpression of USP2-AS1 under hypoxia dramatically increased HCC proliferation and clone formation, whereas the opposite results were observed after USP2-AS1 knockdown."

sparser
"We also found that overexpression of USP2-AS1 increased migration and invasion of HCC cells, while USP2-AS1 knockdown led to the opposite effect."

sparser
"In addition, USP2-AS1 knockdown can increase the efficacy of lenvatinib in our mice tumor xenograft model."

sparser
"Our findings also suggest that USP2-AS1 could increase the protein level of HIF1α by enhancing YBX1 protein binding to HIF1α mRNA under hypoxia and the therapeutic effect of lenvatinib can be enhanced by combination with HIF1α inhibitors in liver cancer."

sparser
"We found that HCC patients with higher USP2-AS1 expression had a worse prognosis."

sparser
"Among these protein molecules, we noticed that YBX1(Y-box binding protein 1) is highly likely to bind to USP2-AS1 with the highest protein spectrum score ( xref )."

sparser
"We confirmed that lncRNA USP2-AS1 promoted the proliferation and invasion of HCC by enhancing YBX1-mediated HIF1α translation under hypoxia."

sparser
"In combination with USP2-AS1 knockdown, the efficacy of lenvatinib increased in a mouse model of subcutaneous liver cancer."

sparser
"USP2-AS1 Is Significantly Up-Regulated in Hepatocellular Carcinoma."

sparser
"Given that lncRNA USP2-AS1 (ubiquitin specific peptidase 2 antisense RNA 1) has the most pronounced fold change in the two categories, so we focused on the role of USP2-AS1 in HCC in our following studies."

sparser
"USP2-AS1 is a long non-coding RNA with 3798 nucleotides in length (USP2-AS1-208, ENST00000659432.1)."

sparser
"Similar to other lncRNAs, we found USP2-AS1 has almost no protein-coding ability by PhyloCSF ( xref )."

sparser
"We also found that USP2-AS1 is likely entirely located in HCC cytoplasm by lncATLAS. ( xref ), which is confirmed by Fluorescent in situ hybridization (FISH) assay ( xref )."

sparser
"To explore the relationship between USP2-AS1 and liver cancer, we analyzed the expression of USP2-AS1 in 36 pairs of HCC and adjacent non-tumor specimens by RT-qPCR."

sparser
"As expected, the expression of USP2-AS1 in HCC was significantly higher than in para-cancer tissues ( xref )."

sparser
"USP2-AS1 was differentially upregulated in hepatoma cell lines (Huh7, MHCC97H, HCCLM3, PLC) compared with normal human hepatocyte LO2 under both normoxic and hypoxic conditions ( xref )."

sparser
"We also found that the expression of USP2-AS1 was significantly up-regulated in these cell lines following 48h hypoxia ( xref ), which was consistent with our RNA sequencing results ( xref )."

sparser
"We designed six truncated probes (corresponding to A-F fragments, respectively) of USP2-AS1, such as A (1-790nt), B (791-1370nt), C (1371-1960nt), D (1961-2450nt), E (2451-3330nt) and F (3331-3798nt) for RNA pulldown assays ( xref and xref )."

sparser
"We demonstrated that fragment A and C are necessary to mediate the binding of USP2-AS1 and YBX1 ( xref )."

sparser
"By analyzing the positive cell rate of USP2-AS1 in human liver cancer tissue microarrays and determining the cutoff value of USP2-AS1 by X-Tile software, we observed that patients with low expression of USP2-AS1 had better prognosis while patients with high expression of USP2-AS1 had shorter OS (Overall Survival) and DFS (Disease-Free Survival) time ( xref )."

sparser
"Notably, clinical information of the tissue microarrays showed that USP2-AS1 remarkably correlated with tumor size and the TNM stage of HCC ( xref )."

sparser
"Importantly, ROC curve analysis showed lncRNA USP2-AS1 had a high AUC (Area Under Curve, 0.824) for HCC diagnosis ( xref )."

sparser
"The above results indicate that hypoxia-related lncRNA USP2-AS1 is up-regulated in HCC."

sparser
"USP2-AS1 positively correlated with worse outcomes in HCC patients and may be a potential prognostic tool."

sparser
"USP2-AS1 Enhances HCC Proliferation, Migration, and Invasion In Vitro Under Hypoxia."

sparser
"To investigate the role of USP2-AS1 in HCC, we constructed stable transfectants of MHCC97H and Huh7 cell lines overexpressing USP2-AS1 and knocked down USP2-AS1 in Huh7 cell lines by lentiviral transfection ( xref )."

sparser
"Under normoxic conditions, overexpression or knockdown of USP2-AS1 did not affect the proliferation, migration, and invasion ability of HCC (data not given)."

sparser
"However, our previous RNA sequencing and FISH experiments have confirmed a significant difference in the expression of USP2-AS1 between liver cancer and para-cancer tissues ( xref )."

sparser
"And given that hypoxia treatment can increase USP2-AS1 expression in HCC cell lines ( xref ), we hypothesized USP2-AS1 promotes the progression of tumors by affecting tumor hypoxic metabolism."

sparser
"These results show USP2-AS1 physically interacts with YBX1 by the A and C fragments under hypoxia."

sparser
"After being treated with hypoxia for 48h, overexpression of USP2-AS1 dramatically increased HCC proliferation and clone formation in vitro ( xref )."

sparser
"Conversely, USP2-AS1 knockdown significantly inhibited the proliferation and clone formation ability of HCC ( xref )."

sparser
"We observed that the migration and invasion of HCC cells decreased after knockdown of USP2-AS1, while the reverse was observed with USP2-AS1 overexpression ( xref )."

sparser
"These results indicate that USP2-AS1 significantly enhances the proliferation, migration, and invasion of liver tumor cells in vitro under hypoxia."

sparser
"USP2-AS1 Physically Interacts With YBX1 Under Hypoxia."

sparser
"The binding of YBX1 to USP2-AS1 was confirmed by YBX1-RIP assay in the MHCC97H cell line ( xref ), and in the Huh7 cell line ( xref )."

sparser
"To investigate how USP2-AS1 binds to YBX1, we predicted the binding site of USP2-AS1 with YBX1 through the online website catRAPID It indicated the segment 500nt-1000nt of USP2-AS1 was likely to bind to YBX1 ( xref )."

sparser
"USP2-AS1 Enhances HIF1α Translation Under Hypoxia."

sparser
"Our previous study showed that USP2-AS1 increased the protein levels of HIF1α in an anoxic environment, RT-qPCR also showed that the expression of target genes downstream of HIF1α was also significantly down-regulated in USP2-AS1 knockdown Huh7 cell line ( xref ), suggesting that USP2-AS1 knockdown may enhance the efficacy of lenvatinib."

sparser
"Therefore, we further explored whether USP2-AS1 knockdown enhanced the therapeutic effect of lenvatinib on HCC in mice tumor xenograft model."

sparser
"Ultimately, 8 lncRNAs (SLC25A30-AS1, HPN-AS1, LINC00607, USP2-AS1, HCG20, LINC00638, MKLN1-AS and LINC00652) were confirmed as hub DElncRNAs in HCC with prognostic signatures by multivariate Cox analysis ( xref and xref )."

sparser
"Importantly, compared with control groups, the tumors’ weight and volume were the smallest in the group treated with lenvatinib and USP2-AS1 knockdown ( xref ), indicating that USP2-AS1 knockdown can enhance the therapeutic effect of lenvatinib in HCC in our mice tumor xenograft model."

sparser
"Our study identified a hypoxia-associated lncRNA USP2-AS1."

sparser
"Based on the multivariate Cox analysis, a PS formula was established using the following equation: PS = (-0.6536 × Exp SLC25A30-AS1) + (-0.5201 × Exp HPN-AS1) + (0.4276 × Exp LINC00607) + (0.6304 × Exp USP2-AS1) + (0.6317 × Exp HCG20) + (0.8265 × Exp LINC00638) + (1.1926 × Exp MKLN1-AS) + (3.0642 × Exp LINC00652)."

sparser
"And we observed USP2-AS1 was significantly up-regulated in HCC compared with normal liver tissue, patients with low expression of USP2-AS1 had better prognosis while patients with high expression of USP2-AS1 had shorter OS and DFS time."

sparser
"Moreover, clinical information showed that USP2-AS1 related with tumor size and the TNM stage of HCC."

sparser
"And ROC curve analysis showed USP2-AS1 had a potential for HCC diagnosis."

sparser
"HPN-AS1 could be utilized in the diagnosis of prostate cancer ( xref ); LINC00607 facilitates the proliferation and invasion of osteosarcoma ( xref ); USP2-AS1 promotes the progression of colon cancer and ovarian cancer ( xref , xref ); and LINC00638 and LINC00652 have been reported in nontumor diseases ( xref – xref ), while no study has revealed the function of the remaining lncRNAs."

sparser
"In vitro and in vivo results, USP2-AS1 knockdown significantly inhibited the growth of HCC, while USP2-AS1 overexpression promoted the proliferation, migration, and invasion ability of liver cancer cells."

sparser
"In addition, we confirmed that USP2-AS1 increases the level of HIF1α protein, by enhancing HIF1α mRNA binding to YBX1 protein under hypoxia."

sparser
"We also observed that USP2-AS1 knockdown decreased the transcript level of some downstream target genes of HIF1α under hypoxia, such as MAPK1, VEGF, MDR1(ABCB1), GLUT1, whose transcriptional activation play an important role in tumor hypoxia metabolism ( xref – xref )."

sparser
"These results suggest that USP2-AS1 promotes the growth and development of HCC by increasing the expression of HIF1α proteins and its downstream target genes."

sparser
"These results suggested that USP2-AS1 mainly promotes placental development by affecting the proliferative activity of placental cells, which may lead to NDFMS."

sparser
"However, further studies are required for the elucidation of the precise molecular mechanisms of USP2-AS1 in the placentas of pregnant women with macrosomia."

sparser
"Our study observed hypoxia-associated lncRNA USP2-AS1 binds to YBX1 protein to enhance its binding to HIF1α mRNA and directly promotes the protein translation of HIF1α ( xref )."

sparser
"Despite USP2-AS1 is up-regulated under hypoxia, USP2-AS1 specifically increases the protein level of HIF1α but not HIF2α, suggesting that the molecular mechanisms of hypoxia metabolism in tumor growth are complex and need further research."

sparser
"The hypoxia-associated lncRNA USP2-AS1 knockdown significantly inhibited the translation of HIF1α protein and the transcriptional activation of its downstream target gene, such as VEGF, and increased the inhibitory effect of lenvatinib on the growth of HCC mice xenograft tumors."

sparser
"In summary, our study identified a hypoxia-associated lncRNA USP2-AS1, which promotes the growth of hepatocellular carcinoma under hypoxia."

sparser
"In mechanism, USP2-AS1 physically interacts with YBX1 to increase the protein translation of HIF1α under hypoxia."

sparser
"We also found that the USP2-AS1 knockdown can enhance the inhibitory effect of lenvatinib on the growth of HCC in our mice tumor xenograft model."

sparser
"Lu et al. [ xref ] identified 892 differentially expressed lncRNAs (763 upregulated and 129 downregulated) based on microarray analysis of lncRNAs in 48 NDFMS and 48 control placentas, which were further validated by selecting lncRNA USP2-AS1 as a candidate lncRNA for subsequent experiments, and the downregulation of lncRNA USP2-AS1 was found to possibly participate in NDFMS development by promoting trophoblast cell viability."

sparser
"LncRNA USP2-AS1."

sparser
"A recent study demonstrated that c-Myc upregulates USP2-AS1 expression by promoting the transcription of lncRNA USP2-AS1."

sparser
"USP2-AS1 stabilizes E2F1 mRNA and increases E2F1 expression by interacting with the RNA-binding protein G3BP1, which in turn attenuates the senescence of HCT116 and A549 cells and serves a pro-cancer function of c-Myc ( xref )."

sparser
"Recently, the biological and clinical significance of lncRNA USP2-AS1 have been investigated in colon adenocarcinoma."

sparser
"The expression of ubiquitin-specific peptidase 2 antisense RNA 1 (lncRNA USP2-AS1), a USP2-specific antisense RNA, is significantly higher in HCC tissues than in paraneoplastic tissues."

sparser
"The high expression of USP2-AS1 is significantly associated with a poorer prognosis."

sparser
"Knockdown of USP2-AS1 promotes the ubiquitin-mediated degradation of Y-box binding protein 1-mediated hypoxia-inducible factor 1α; inhibits the proliferative, migratory and invasive abilities of HCC cells and reduces the tumorigenicity of HCC cells in mice ( xref )."

sparser
"USP2-AS1 can compete for endogenous RNAs to regulate the expression of downstream genes by sponging miRNAs ( xref )."

sparser
"Findings showed that in 43 patients with CRC, the USP2-AS1 expression was significantly higher in the tumor tissues, and its level was associated with tumor grade and stage [ xref ] ."

sparser
"Some of the identified lncRNAs were highly subgroup-specific, such as lnc-CCL2-2, lnc-ABCE1-5, USP2-AS1 (GP-3-MB), and lnc-TBC1D16–3 (GP-4-MB)."

sparser
"Guo et al ( xref ) investigated the specific molecular mechanisms through which USP2-AS1 promotes ovarian cancer progression."

sparser
"Previously, it was shown that two transcripts of USP2-AS1 bind to YAP1 [ xref ] ."

sparser
"USP2-AS1 and miRNA-520d-3P were found to bind to each other, and silencing of miRNA-520d-3P reversed the USP2-AS1 -induced proliferative, migratory and invasive abilities of ovarian cancer cells."

sparser
"Li et al. confirmed that these two transcripts of USP2-AS1 bind to YAP1 in colon adenocarcinoma cell lines SW480, SW620, and Lovo."

sparser
"The specific mechanism is related to the involvement of USP2-AS1 in the ubiquitinated degradation of miRNA-520d-3P downstream gene KIAA1522 ."

sparser
"Therefore, USP2 and USP2-AS1 may serve as potential targets for the treatment of ovarian cancer."

sparser
"In addition, the expression of USP2-AS1 is significantly elevated in clinical colon adenocarcinoma tumor tissues and is positively correlated with tumor size, grade and TNM stage."

sparser
"Knockdown of USP2-AS1 can promote phosphorylation and ubiquitin-mediated degradation of Yes-associated protein 1 (YAP1) to inhibit the activation of the Hippo/YAP1 signaling pathway, which in turn inhibits the proliferative, migratory and invasive abilities of tumor cells and reduces the tumorigenicity and distant metastatic ability of cancer cells in mice ( xref )."

sparser
"The in vitro and in vivo experiments revealed that USP2-AS1 overexpression enhanced colon adenocarcinoma cell proliferation, invasion, and metastasis."

sparser
"Moreover, USP2-AS1 overexpression decreased the p -LATS1, LATS1, LATS2, and p-YAP1 levels and increased total YAP1 level in colon adenocarcinoma cell lines."

sparser
"The second module consisted of one DEM (PDSS1), three DEMis (hsa-miR-145-5p, hsa-miR-212-3p and hsa-miR-132-3p), and two DELs (AL035425.3 and USP2-AS1) ( xref )."

sparser
"The Hippo pathway target genes, CTGF, CYR61, and SOX9 were inhibited by USP2-AS1 knockdown, and vice versa, which was in accordance with the effect of USP2-AS1 overexpression on inactivation of Hippo pathway[ xref ] ."

sparser
"In addition, USP2-AS1 promotes progression through proliferation, tumor growth, invasion, and the transition from G0/G1 to the S phase of the cell cycle in both in vitro and in vivo models [ xref ]."

sparser
"Xu et al. found the cuproptosis genes FDX1, PDHA1, and DLAT were remarkably down-regulated in BC tissues, furthermore, they identified a unique model BCCuS based on cuproptosis-related 2-lncRNAs USP2-AS1 and NIFK-AS1 for BC prediction xref ."

sparser
"Additionally, the function of lncRNA ubiquitin-specific peptidase 2 antisense RNA 1 ( USP2-AS1 ) was investigated using a trophoblast cell line."

sparser
"In addition, a significant downregulation in the levels of lncRNA USP2-AS1 was observed in both the microarray data and second-stage verification."

sparser
"The overexpression of lncRNA USP2-AS1 induced G1 phase cell cycle arrest and the number of cells entering S phase was reduced."

sparser
"In addition, lncRNA USP2-AS1 has been demonstrated to be upregulated in ovarian cancer."

sparser
"Mechanistic analysis have revealed that USP2-AS1 promotes ovarian cancer progression via the miR-520d-3p/KIAA1522 axis ( xref )."

sparser
"In addition, the viability of HTR-8/SVneo cells was significantly inhibited when lncRNA USP2-AS1 was overexpressed."

sparser
"Therefore, these findings demonstrated that lncRNAs were significantly differentially expressed in the placentas of pregnant women with NDFMS and that the downregulation of lncRNA USP2-AS1 may be involved in the pathogenesis of NDFMS, by promoting trophoblast cell viability."

sparser
"Previous studies have reported that lncRNAs may potentially participate in the pathogenesis of placental development ( xref – xref ); however, the specific biological effects of lncRNAs remain largely unknown, particularly concerning the regulatory role of ubiquitin-specific peptidase 2 antisense RNA 1 ( USP2-AS1 ) in NDFMS."

sparser
"Furthermore, the function of lncRNA USP2-AS1 was investigated using HTR-8/SVneo, a trophoblast cell line."

sparser
"Among these, ubiquitin-specific peptidase 2 antisense RNA 1 ( USP2-AS1 ) demonstrated a significantly decreased expression in both microarray and two-stage RT-qPCR verification results."

sparser
"Therefore, USP2-AS1 was selected as the candidate lncRNA for the subsequent experiments."

sparser
"Effects of lncRNA USP2-AS1 on human chorionic trophoblasts."

sparser
"In the present study, HTR-8/SVneo cells were used to elucidate the role of lncRNA USP2-AS1 in placental development."

sparser
"The transfection efficiency of lncRNA USP2-AS1 was first examined."

sparser
"Compared with the control group, the USP2-AS1 expression levels in HTR-8/SVneo cells in the USP2-AS1 overexpression group were significantly increased following transfection ( xref )."

sparser
"The overexpression of lncRNA USP2-AS1 arrested the cells in the G1 phase and reduced the number of cells entering the S phase ( xref )."

sparser
"lncRNAs have also been revealed to play vital biological regulatory effects in the development of the placenta ( xref – xref ); however, the role and mechanisms of action of USP2-AS1 in NDFMS remain unclear."

sparser
"Following USP2-AS1 overexpression, the cells were blocked in the G1 phase, and the cell viability and apoptotic rates were decreased."

sparser
"The overexpression of lncRNA USP2-AS1 also significantly decreased cell viability ( xref )."

sparser
"However, the overexpression of lncRNA USP2-AS1 significantly decreased cell apoptosis compared with the control group ( xref )."

sparser
"In addition, lncRNA USP2-AS1 exhibited a significant downregulation in both the microarray data and second-stage RT-qPCR verification."

sparser
"Therefore, lncRNA USP2-AS1 was the most prominent candidate lncRNA, and was used for subsequent analysis."

sparser
"lncRNA USP2-AS1 , located on the human chromosome 11q23.3, is a lncRNA with a length of 2,486 nucleotides."

sparser
"A previous study revealed that USP2-AS1 promotes the growth and metastasis of colon adenocarcinoma cells and may play a carcinogenic effect in colon adenocarcinoma ( xref )."

sparser
"It was hypothesized that the decrease in the apoptosis of HTR-8/SVneo cells overexpressing USP2-AS1 may have been a compensation effect."