IndraLab

Statements

SMAD3 is methylated. 92 / 92
| 1 91
sparser
"Due to smoking and the anatomical location of the SCC in the proximal airways, which allows for greater exposure to cigarette smoke particles, cigarette smoke condensates selectively increase SMAD3 promoter methylation, exposing SCC-TAFs to stronger epigenetic suppression of SMAD3."
37685308
sparser
"This result suggests that the histotype-specific regulation of lung cancer tumour fibrosis is mediated by differential levels of SMAD3 promoter methylation in TAFs."
37685308
sparser
"Among them, SMAD3 methylation in the neonates with maternal asthma was strongly and positively associated with neonatal production of cord blood mononuclear cell-derived IL-1β, an innate inflammatory mediator."
31905427
sparser
"Another study demonstrated that EZH2-mediated methylation of SMAD3 at K53/K333 can drive cancer metastasis [ xref ]."
38834851
sparser
"Moreover, we evaluated the impact of SMAD3 methylation expression on the survival prognosis using the GSCA database."
39753728
sparser
"Augmented methylation of SMAD3 in cord blood mononuclear cells of newborns, which was associated with the inflammatory regulator IL-1b, determined whether or not the subjects, all with asthmatic mothers, would develop asthma by age 9 [ xref ]."
33781317
sparser
"The results were rather promising, demonstrating that high SMAD3 methylation expression tended to predict a more favorable prognosis in nearly all statistically significant prognostic analyses (Fig.  xref C, Supplementary Fig. 3SD-G)."
39753728
sparser
"It was shown that the reduced fibrosis and nintedanib response in SCC-TAFs compared to ADC-TAFs was associated with increased promoter methylation of SMAD3."
37685308
sparser
"Further researches are needed to elucidate the potential function of SMAD3 methylation in different cancers."
39753728
sparser
"Unlike EDARADD , no prognostic information was observed in SMAD3 or CHI3L1 methylation status in the same data sets (, available at Carcinogenesis Online)."
26449251
sparser
"Pretreatment with a specific PRMT5 inhibitor EPZ015666 (5 nM) or overexpression of a catalytically inactive mutant of PRMT5, PRMT5(E444Q), reduced PRMT5-induced methylation of Smad3, thus suppressing PRMT5-mediated cardiac fibroblast activation in vitro."
36056082
sparser
"Exposure to cigarette smoke particles and condensation of these particles in the proximal airways enhance SMAD3 promoter methylation leading to SMAD3 suppression xref ."
38589525
sparser
"Mechanistically, the reduced fibrosis and nintedanib response of SCC-TAFs were associated with increased promoter methylation of the pro-fibrotic TGF-β transcription factor SMAD3 compared to ADC-TAFs, which elicited a compensatory increase in TGF-β1/SMAD2 activation."
31694906
sparser
"DNA methylation in cord blood mononuclear cells from the participants of the Infant Immune Study identified SMAD3 methylation as associated with asthmatic children whose mothers were also asthmatic [ xref ]."
35055381
sparser
"A reduction in the methylation of SMAD3 in circulating cell-free was detected in 70% of CRC patients, but in only 20% of healthy individuals."
37685308
sparser
"It is reported that the changes of the methylation of SMAD3 and SMAD6 were correlated with gene transcription levels in CKD samples [ xref ]."
34462056
sparser
"Importantly, the finding that SMAD3 methylation patterns are increased at birth in children who develop asthma at age 9 suggests that progression towards asthma may begin in utero [ xref ]."
32887352
sparser
"Of the large number of DNA methylation changes they identified, increased methylation in SMAD3 was: (1) associated with childhood asthma risk, a result that was replicated in two independent cohorts; (2) was the most connected node within the network of asthma-associated DMRs; and (3) was strongly and positively associated with neonatal production of IL-1β, an innate inflammatory mediator."
29389731
sparser
"Additionally, our analysis of SMAD3 methylation patterns in human cancers unveiled a favorable prognosis linked to elevated DNA methylation levels in pan-cancer."
39753728
sparser
"Conversely, in seven tumor groups (LUAD, LUSC, TGCT, CHOL, THCA, BLCA, LIHC), the SMAD3 methylation levels were significantly lower than those observed in normal groups."
39753728
sparser
"Our results also support that smoking and/or the anatomic location of SCC in the proximal airways, which are more exposed to cigarette smoke particles, may prime SCC-TAFs to stronger SMAD3 epigenetic repression, since cigarette smoke condensate selectively increased SMAD3 promoter methylation."
31694906
sparser
"Our results unveil that the histotype-specific regulation of tumor fibrosis in lung cancer is mediated through differential SMAD3 promoter methylation in TAFs, and provide new mechanistic insights on the selective poor response of SCC-TAFs to nintedanib."
31694906
sparser
"For example, SMAD3 and SMAD6 methylated changes were correlated with their transcriptional levels in samples of CKD pateints. xref The RAS protein activator-like 1 (RASAL1) hypermethylation was related to kidney fibrosis with the perpetuation of myofibroblast activation, where TGF-β mediated the hypermethylation of RASAL1 with DNMT1 effect in fibrogenesis. xref In whole-kidney biopsy and fibroblasts, hypermethylation and transcriptional silencing of RASAL1 was also related to severe fibrosis."
36932062
sparser
"Interestingly, we observed that both SMAD2 and SMAD3 were differentially methylated in OA patients compared to controls, indicating that epigenetics is a driving force in this shift."
24838673
sparser
"The SMAD3 methylation level in CRC tumors, which was half that of adjacent normal colorectal tissue, was defined as hypomethylation."
33036415
sparser
"No study has focused on the relationship between the SMAD3 methylation level and CRC diagnosis."
33036415
sparser
"However, the role of SMAD3 methylation in cancer is still unclear."
33036415
sparser
"Correlation between Prognosis and SMAD3 Methylation Level."
33036415
sparser
"We investigated whether SMAD3 methylation is associated with survival in CRC."
33036415
sparser
"We stratified the overall survival of Taiwanese patients with CRC and patients in TCGA datasets into two subsets on the basis of SMAD3 methylation: low hypomethylation and no-hypomethylation groups."
33036415
sparser
"Allele-specific DNA methylation of SMAD3 is regulated based on genetic effects relevant to disease susceptibility."
33036415
sparser
"DNA methylation of SMAD3 was analyzed in 38 paired colorectal samples and 314 tumor sample datasets from TCGA."
33036415
sparser
"Thus, circulating methylated SMAD3 cannot distinguish patients from healthy participants in a plasma volume of 200 μL. As evidenced by previous studies, the column-based method may lead to cross-contamination [ xref , xref ]."
33036415
sparser
"In addition, combining SMAD3 with other hypomethylated genes, such as ACOT7 , RASA3 , B3GNTL1 , PIGB , MAP3K5 , LPIN1 , and MYBPC3 , which are potential biomarkers of CRC in the analytical model, may improve accuracy, increase sensitivity, and reduce false-positive results when predicting CRC in circulating methylated SMAD3 ."
33036415
sparser
"In conclusion, SMAD3 methylation levels vary in colorectal tissue based on the type of cancer."
33036415
sparser
"Methylation levels measured by bisulfite sequencing over the entire DNA (Spearman correlation coefficient [ρ = 0.48], p = 1.2 × 10−13) and at intermediate DNA methylation levels (8%–92%, p = 0.006), SMAD3 methylation was extremely correlated with asthma (ρ = 0.46, p = 0.009). xref "
38043345
sparser
"Moreover, reduced fibrosis, as well as the reduced nintedanib response of LUSC-related CAFs as compared with LUAD-related CAFs, were found to be associated with the increased promoter methylation of the profibrotic TGF-β transcription factor SMAD3."
36422541
sparser
"Fetal epigenetic regulation is modifiable by the maternal environment and has been proposed as a mechanism by which prenatal environmental stimuli contribute to the development of respiratory disorders. xref In support of this notion, mechanistic animal studies have demonstrated that maternal microbial exposures, through DNA methylation and histone modifications, may modulate the expression of important immune factors such as interleukin (IL-4) and interferon-γ genes in the offspring’s lungs. xref , xref Increases in histone H3 acetylation linked to an asthma phenotype have been also identified in mice pups after maternal nicotine exposure. xref In humans, epigenetic modifications (e.g., SMAD3 methylation) have been proposed as a mechanism mediating the intergenerational risk of asthma in children from asthmatic mothers. xref Furthermore, epigenetic modifications may also mediate the effect of noninheritable prenatal factors on respiratory outcomes."
34388306
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"While the Hdac4 methylation localized within CCWGG, the Smad3 and Mid1 methylations were present at CCGG motifs within intronic enhancers."
32926553
sparser
"In particular, DNAJA4 , TFR2 , SMAD3 , PLAG1 , FGF1 and HNF4A methylation represent novel and possibly physiologically relevant markers of neonatal adiposity."
31851703
sparser
"We demonstrated that PRMT5-overexpression enhanced methylated-Smad3 levels in vivo and in vitro."
36056082
sparser
"Other studies indicated that increased EZH2 expression abnormally increased SMAD3 methylation, thereby activating SMAD3."
38514720
sparser
"Clinically, researchers demonstrated that SMAD3 methylation was significantly associated with poor survival of patients with breast cancer xref ."
38514720
sparser
"In terms of treatment, targeted methylation of SMAD3 can inhibit tumor cell metastasis."
38514720
sparser
"Notably, we also reported that stimulating normal pulmonary fibroblasts with cigarette smoke condensate in culture was sufficient to time- and dose-dependently increase the promoter methylation of SMAD3 but not that of its closely related homolog SMAD2 [ xref ], as summarized in xref A–C. Although the underlying mechanisms of the selective SMAD3 hypermethylation remains unclear, it is conceivable that the common DNMT1 increase in smokers may be involved."
34359678
sparser
"In another study on Chinese Uygur population by the same group, methylation of the gene Smad3 is reported."
34498177
sparser
"In children born to asthmatic mothers, SMAD3 methylation at birth was associated with childhood asthma risk and was more prominent in asthmatic mothers [ xref ]."
31776749
sparser
"In a study on newborns, SMAD3 methylation in asthmatic mothers was linked to a higher risk of the newborns developing asthma in childhood [ xref ]."
37629446
sparser
"Nevertheless, there is currently no information available regarding the DNA methylation of SMAD3 in PNETs."
38279330
sparser
"SMAD3 methylation in IIS (n=60) and in two replication cohorts (The Manchester Asthma and Allergy Study, n=30, and the Childhood Origins of ASThma Study, n=28) was analyzed by bisulfite sequencing or Illumina 450K arrays."
28011059
sparser
"We investigated the relationship between Smad3 gene methylation and pulmonary fibrosis in pigeon breeder's lung (PBL)."
28562330
sparser
"In all three cohorts, methylation in SMAD3 , the most connected node within the network of asthma-associated DMRs, was selectively increased in asthmatic children of asthmatic mothers and was associated with childhood asthma risk."
28011059
sparser
"Smad3 gene methylation and Smad3 mRNA expression were negatively correlated, with a correlation coefficient of -0.84."
28562330
sparser
"Smad3 methylation, Smad3 mRNA expression and TGF-β level were correlated with the number of pigeons bred by patients."
28562330
sparser
"Moreover , SMAD3 methylation in IIS neonates with maternal asthma was strongly and positively associated with neonatal production of IL-1β, an innate inflammatory mediator."
28011059
sparser
"Previously, we conducted a preliminary screening analysis of whole-genome methylation in 4 cases of Uygur PBL and 4 Uygur pigeon breeders without this disease using the Illumina 450K method (Illumina 450K Infinium Methylation BeadChip; SHBIO, Shanghai, China), and the results showed abnormal methylation of the Smad3 gene among the Uygur PBL patients."
28562330
sparser
"Smad3 methylation."
28562330
sparser
"Mean SMAD3 methylation levels at birth were 41.3% (95% CI 35.5–47.5) in non-asthmatics and 47.1% (95% CI 40.6–53.1) in asthmatics, a difference that did not reach statistical significance ( P =0.2 by Wilcoxon two-sample test: xref )."
28011059
sparser
"When the relation between SMAD3 methylation at birth and childhood asthma was examined separately in children with and without maternal asthma, SMAD3 methylation was found to be significantly increased in asthmatic compared to non-asthmatic children of asthmatic mothers ( P =0.005 by Wilcoxon two-sample test)."
28011059
sparser
"Of interest, SMAD3 DNA methylation has also been associated with atopic asthma (at age 5 years) in a study of children with a history of severe adenovirus-induced wheezing in infancy ( xref )."
31001502
sparser
"Given these findings, the objective of this study was to assess a larger sample to further investigate the relationship between Smad3 gene methylation and pulmonary fibrosis in Uygur PBL patients."
28562330
sparser
"After constructing a genomic methylation analysis for patients with PBL and detecting abnormal Smad3 gene hypomethylation, we hypothesized that pulmonary fibrosis in patients with PBL is correlated with Smad3 gene methylation."
28562330
sparser
"Correlations of Smad3 gene methylation and Smad3 mRNA expression with the extent of pulmonary fibrosis."
28562330
sparser
"Although associations between SMAD3 variants [rs17228058 ( xref ), rs744910 ( xref ), rs17294280 ( xref )] and asthma have been reported in GWAS, asthma-related SMAD3 methylation differences were unlikely to be influenced by SMAD3 genotype."
28011059
sparser
"The level of Smad3 gene methylation, mRNA expression, and the extent of pulmonary fibrosis in patients with PBL were analyzed based on Pearson correlation coefficients."
28562330
sparser
"In contrast, asthmatic and non-asthmatic children of non-asthmatic mothers did not differ in their SMAD3 methylation levels [ P for interaction (by linear regression) = 0.001; xref ]."
28011059
sparser
"Most importantly, the SMAD3 methylation differences detected between asthmatic and non-asthmatic children of asthmatic mothers remained significant ( P =0.04 by Wilcoxon two-sample test) even after adjusting for CBMC composition ( xref )."
28011059
sparser
"Finally, we asked whether the SMAD3 methylation levels measured at birth in children of asthmatic mothers are associated with risk for childhood asthma in our three cohorts."
28011059
sparser
"A meta-analysis revealed that for each 10% increase in SMAD3 CpG7 methylation there is nearly a two-fold increased risk of childhood asthma (meta-analysis Odds Ratio=1.95, [95%CI: 1.23, 3.10], P =0.005; heterogeneity P =0.5)."
28011059
sparser
"Our study found that Smad3 was involved in the development of pulmonary fibrosis in patients with PBL and that Smad3 gene methylation was the cause of abnormal Smad3 mRNA expression."
28562330
sparser
"Therefore, we relied again on the IIS to explore the relationship between neonatal LPS-induced IL-1β production, SMAD3 promoter methylation and childhood asthma."
28011059
sparser
"The distributions of SMAD3 methylation and log IL-1β production in non-asthmatic and asthmatic children without and with a maternal history of asthma were compared by dividing mean percentage SMAD3 methylation and log IL-1β secretion at the median, thereby creating four groups (low/low, low/high, high/low and high/high)."
28011059
sparser
"These results suggest that a strong relationship exists between neonatal SMAD3 methylation, production of the innate cytokine IL-1β, and childhood asthma."
28011059
sparser
"Maternal asthma modifies the relation between neonatal SMAD3 methylation and IL-1ββ β producing capacity."
28011059
sparser
"While it is unclear whether these mechanisms operate pre- and/or perinatally, detection of the relationship between SMAD3 methylation and IL-1β production selectively among children of asthmatic mothers implies that the in utero environment is critical for directing the epigenetic trajectory towards childhood asthma."
28011059
sparser
"In contrast, the children of asthmatic mothers who developed asthma were almost entirely found among those with high SMAD3 promoter methylation and high IL-1β secretion ( P =0.009 by Fisher’s Exact Test; xref )."
28011059
sparser
"Previous studies, both in China and in other countries, have mainly focused on the relationship between Smad3 and fibrosis, and no prior investigation has reported the abnormal expression of Smad3 with respect to methylation of the Smad3 gene."
28562330
sparser
"The aim of the study was to evaluate promoter methylation of CDKN1 , CDKN2A , MYC , Smad3 , SP1 , and UBC genes in tumor tissue of HNSCC patients."
38540340
sparser
"These findings indicated that the DNA methylation of TERT, DDAH2, DNMT3B, MAD1L1, NOTCH1, TP53BP1, MAP2K1, SMAD2, SMAD3, SMAD6 , and SREBF1 significantly impacted their gene expression levels."
39215079
sparser
"EZH2 triggers SMAD3 methylation to promote the interaction between SMAD3 and its cell membrane locator, maintaining SMAD3 phosphorylation of TGFβ receptors and facilitating breast cancer metastasis. xref EZH2 also induces ribosomal synthesis overactivation and ribosomal DNA instability by silencing PHACTR2-AS1 to accelerate breast cancer metastasis. xref EZH2 induces methylation of lysine K362 in ERG, which is beneficial for DNA binding and increases ERG transcriptional activity, thereby enhancing the invasiveness of ERG fusion prostate cancer. xref , xref EZH2 silences primary cilia genes and activates the Wnt pathway to promote melanoma metastasis. xref "
38438349
sparser
"Some genes were associated with known secondary traits: rs7497064 ( SMAD6 -methylation associated) and rs731758 ( NF1 -methylation associated) were linked to secondary traits such as height, weight, and body fat metabolic rate; rs2736100 ( TERT -methylation related) was associated with lung cancer, glioma, and testicular germ cell tumors; rs1270942 and others ( DDAH2- methylation related) were associated with multiple traits such as asthma, lung cancer, hyperthyroidism, systemic lupus erythematosus, diabetes, and schizophrenia; rs12945438 and rs8078675 ( KCNJ12 -methylation related) were associated with body mass index; rs6087989 ( DNMT3B -methylation related) was associated with immune cell counts; rs7783715 and rs11761270 ( MAD1L1 -methylation related) were associated with schizophrenia; rs10744826 ( MVK -methylation related) was associated with cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), etc.; rs17293632 ( SMAD3 -methylation related) was associated with coronary artery disease, asthma, and other allergic diseases; and rs4938784 and rs4938792 (LAYN protein expression related) were associated with allergic rhinitis, asthma, and other diseases."
39215079
sparser
"In the latter study, differential methylation of SMAD3 (SMAD family member 3) was found to be particularly associated with asthma [ xref ]."
| PMC
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"Bisulfite sequencing of cord blood cell DNA from our IIS neonates and two replication cohorts (The Manchester Asthma and Allergy Study, and the Childhood Origins of ASThma Study) showed that SMAD3 promoter methylation at birth was selectively and significantly increased in asthmatic children of asthmatic mothers and was associated with childhood asthma risk."
29709672
sparser
"Additionally, SMR analysis indicated that SMAD6, TERT, DDAH2, TP53BP1, NOTCH1, DNMT3B, MAD1L1, SMAD2 , and SMAD3 methylation levels may have influenced gene expression."
39215079
sparser
"Methylation of SMAD3 at birth, a locus previously identified by GWAS and known to regulate FOXP3 induction during Treg development ( xref ) was also found to be strongly associated with the development of childhood asthma, potentially through a dysregulation of IL-1b signaling ( xref )."
35693821
sparser
"Moreover, CBMCs of asthmatic children from asthmatic mothers secreted more of IL-1β and exhibited high SMAD3 methylation as compared to non-asthmatic children from asthmatic mothers ( xref )."
35693821
sparser
"They found that methylation of the SMAD3 gene at birth was associated with increased risk for developing childhood asthma.( xref ) Another EWAS that also examined DNA methylation signals in cord blood cells, but in different cohorts, found 9 CpGs and 35 regions in newborns that were differentially methylated and associated with asthma development; these loci may represent predictive biomarkers of asthma risk by childhood.( xref ) These two studies indicate that DNA methylation patterns at certain loci present at birth are associated with asthma development later in life."
37295475
sparser
"The cis-acting element methylation of HDAC4, SMAD3, and MID1 may play a regulatory role during palatal fusion."
30277813
sparser
"Dimopoulos and colleagues showed that acquired IMiD resistance is associated with an increase in genome-wide DNA methylation and downregulation of SMAD3."
30555699
reach
"Therefore, Smad3 gene hypomethylation may be caused by long-term exposure to allergen sources; an increase in levels of TGF-beta, an upstream factor of Smad3; or interactions between these two factors."
28562330
sparser
"Similarly, altered methylation of TGFB2 and SMAD3 , components of the transforming growth factor-beta (TGF-β) signaling pathway, has been linked to abnormal aortic remodeling and aneurysm formation [ xref ]."
| PMC
sparser
"We revealed that Akt K64 methylation was critical for Akt activation and tumorigenesis, while mothers against decapentaplegic homolog 3 (SMAD3) methylation was crucial for TGF-β pathway activation and cancer metastasis. ( xref – xref )."
37235656