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KRAS increases the amount of KRAS. 43 / 56
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"Compared to the unmodified WT cells, KI of KRAS enhancer variant (chr12 :25538881 : C> T) increased the baseline KRAS expression in DMSO treated KI-Mut cells (2.7 and 2.2-fold, P < 0.001; XREF_FIG)."
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"23 However, the KRAS variant is associated with a BRCA1 mutation like gene expression signature, supporting the notion that there might be increased oncogenic risk in the presence of the KRAS variant and high KRAS expression and low BRCA1 expression, either through mutation or other mechanisms."
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"Liu et al. confirmed that KRAS gene SNP rs8720 CT increased mRNA and protein expression of KRAS and thus contribute to increased colorectal carcinoma (CRC) risk and reduced survival (41)."
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"Western blotting revealed that the expression of KRAS and beta-catenin was eliminated by DDX3 or KRAS silencing, but KRAS expression was unchanged by LY294002, shDDX3 plus KRAS or shDDX3, LY294002 plus KRAS treatments in CCM2 cells."
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"Previous studies have provided preliminary evidence that the KRAS G4 can indeed be targeted with small molecules to elicit changes in KRAS expression."
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"reported interaction between the Myc associated zinc-finger protein MAZ and the G-quadruplex motif present in the promoter of murine KRAS resulting in activation of KRAS expression."
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"A fraction of oncogenic Kras induced T-ALL and MPN lose wild-type Kras expression."
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"Notably, overexpression of exogenous WT KRAS did not elicit additional tumor-suppressive effects in pancreatic cancer cells with endogenous WT KRAS expression (Fig. S4), signifying that it’s the presence of the WT allele, more than the dosage, that is more pertinent to its tumor-suppressive functions."
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"In contrast, while knockdown of wild-type KRAS did not significantly reduce KRAS protein expression in H358 cells, mutant specific knockdown potently and specifically reduced KRAS protein expression."
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"Indeed, there was a decent reduction in c-MYC nuclear stain in case of C-KRAS-esiRNA treatment of DLD1 tumors (XREF_FIG), meanwhile KRAS levels were also reduced by KRAS knockdown (XREF_FIG)."
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"Recent studies have identified a KRAS 3 ' UTR polymorphism (rs61764370), aT-to-G nucleotide change in the 6th LCS (LCS6), that was found to increase KRAS expression by altering let-7 binding capability to the KRAS mRNA [XREF_BIBR]."
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"Kras G12D/+ mice were treated with AdCre to initiate expression of oncogenic Kras."
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"In addition, Morpholino knocked-down zebrafish embryos of kras caused heart and craniofacial malformations, and expression of mutated kras resulted in maldevelopment of the heart."
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"LCS6 in the KRAS 3 '-UTR mRNA causes an increase in expression of KRAS in vitro and a reduction in let-7 levels in vivo (Chin et al., 2008)."
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"KRAS protein functions as a molecular switch cycling between ON and OFF state to affect the intracellular signaling.30 Whereas the ON switch to the active state is promoted by guanine nucleotide exchange factors (GEFs), the OFF state is regulated by GTPase-activating proteins (GAPs).33 Oncogenic alleles of KRAS lose the capability of GAP-induced GTP hydrolysis resulting in increased GTP-bound KRAS protein levels which in turn trigger the pro-growth signaling pathways."
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"KRAS siRNA effectively reduced KRAS expression, resulting in marked inhibition of p-ERK (XREF_FIG and XREF_SUPPLEMENTARY)."
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"Western blot analysis confirmed that KRAS transfection increased KRAS expression in silibinin treated cells."
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"KRAS is upregulated in many cancers, and mutations in the KRAS gene can cause expression of aberrant KRAS proteins that promote the transformation of normal cells into cancerous cells by promoting cellular proliferation, survival, and cancer progression [88]."
| PMC
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"XREF_BIBR, XREF_BIBR KRAS MASI may lead to elevated KRAS mRNA levels 24 and increased RAS activity in murine pancreatic adenocarcinomas and other carcinomas."
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"We found that all 3 T-ALL cell lines derived from oncogenic Kras mice and ~ 25% of oncogenic Kras induced T-ALL specimens lost WT Kras expression through distinct mechanisms (XREF_FIG)."
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"Inhibition of KRAS expression by selected KRAS antisense oligonucleotides has been shown to be associated with significantly reduced secretion of VEGF-A165 into the medium of colorectal cancer cell cultures [XREF_BIBR]."
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"We also identified that a fraction of oncogenic Kras induced MPN lost WT Kras expression, at both early and late stages of MPN development (XREF_FIG)."
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"By demonstrating that the KRAS enhancer variant confer gain-of-function activity to promote KRAS expression in leukemia cells, our results provide a mechanism that may explain the lack of KRAS hotspot coding mutations compared to other RAS family proteins such as NRAS."
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"Western blotting indicated that the expression of KRAS, YAP1, and HIF-1alpha in SNU-C1 cells was almost completely eliminated by DDX3 manipulation, KRAS silencing, or treatment with the ROS scavenger N-acetylcysteine (NAC)."
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"Aim : KRAS SNPs may increase KRAS transcription and KRAS levels."
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"As shown in XREF_FIG, the mRNA and protein levels of KRAS were notably promoted by KRAS overexpression and were inhibited by KRAS silencing compared with the pEX and shNC groups, respectively (p < 0.01)."
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"These data indicated that upregulated H3 K27M might be a potent treatment target for diffuse midline glioma, H3 K27M-mutant exhibiting MASI of H3F3A K27M.There were previous studies where KRAS MASI elevated KRAS mRNA levels, increasing RAS activity [14, 24] and wild-type allele of KRAS has also been shown to play a pivotal role as a tumor suppressor [25]."
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"In humans, a change in codon composition in the gene KRAS, from rare to common codons, increases KRas protein expression and is associated with tumorigenicity."
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"A homologous promoterless K-ras cDNA targeting endogenous K-ras expression inhibits human pancreatic cancer cell growth in vitro and in vivo."
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"Based on the gene knockdown results in Figure XREF_FIG, HDAC1 siRNA and K-Ras siRNA delivered by FA/GO nanoformulations could efficiently suppress the expression of HDAC1 and K-Ras, respectively."
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"miR-199a reduced K-RAS expression significantly, and forced expression of K-RAS restored K-RAS expression as shown in Figure 5A."
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"Chen et al reported that as premiR-143-3p is transfected in LoVo and SW480 CRC cell, KRAS expression is significantly reduced by the inhibition of KRAS mRNA in the translational level."
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"In the four cell lines where KRAS siRNA strongly suppressed KRAS expression, we observed substantial reductions in pERK as well as in MYC protein levels (Fig. 6C), indicating a shared role of MYC in the oncogenic function of both G12 and Q61 mutants."
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"KRAS, the key regulator of RAS and ERK pathway, was tightly regulated by enzyme activity of SIRT1, SIRT1 deacetylated KRAS and increased the expression of KRAS (Cheng et al., 2015a)."
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"Oncogenic mutations in KRAS typically occur at hotspots in the protein (e.g., codons 12, 13, and 61), increasing the steady-state levels of KRAS proteins in the GTP-bound state that are capable of driving protumorigenic signaling through downstream effector pathways, such as the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways."
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"KRAS siRNA sequences induced> 90% knockdown of KRAS expression, significantly reducing viability in mutant cell lines."
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"Kras shRNA molecules reduce the expression of both WT Kras and Kras G12D and more potent constructs than shKras.54 inhibited the growth of AML 101-R (data not shown)."
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"In the patients with metastatic CRC, a polymorphism rs1764370 in KRAS leads to loss function of let-7, increased expression of KRAS, and drug resistance of cetuximab-irinotecan chemotherapy, as well as reduced overall survival and progression-free survival 15."
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"These experiments revealed that K-Ras V12 induced a time- and concentration dependent increase in KRAS protein levels that was accompanied by an increase in DCF-fluorescence and binucleated cells."
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"Gnat3-null (Gnat3 -/-) mice were crossbred with animals harboring a Cre inducible Kras LSL-G12D/+ allele with either Ptf1a Cre/+ (KC) or tamoxifen inducible Ptf1a CreERT/+ (KC ERT) mice to drive oncogenic KRAS expression in the pancreas."
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"Compared to the wild-type T genotype, the less-frequent variant G transcript of KRAS exerts a high stability through escaping the let-7 translational repression and causes a high level of KRAS in the cell."
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"In previous studies, it has been shown that KRAS variants of RS61764370 interfere with the binding of Let-7 miRNA and increase the expression of KRAS XREF_BIBR."
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"The authors speculated that the rare codon usage in KRAS leads to low endogenous protein levels, meaning that oncogenically activated KRAS would not be expressed highly enough to induce the senescent phenotype."
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