scholarly journals Downregulation of microRNA‑126 is inversely correlated with insulin receptor substrate‑1 protein expression in colorectal cancer and is associated with advanced stages of disease

2020 ◽  
Vol 20 (3) ◽  
pp. 2411-2419
Author(s):  
Shicai Ye ◽  
Caiyuan Yu ◽  
Guixia Zhang ◽  
Feixiong Shi ◽  
Yongze  Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Insulin Receptor ◽  
Insulin Receptor Substrate ◽  
Insulin Receptor Substrate 1 ◽  
Advanced Stages

scholarly journals Gly972Arg Variant of Insulin Receptor Substrate 1 Gene and Colorectal Cancer Risk in Overweight/Obese Subjects

2016 ◽  
Vol 31 (1) ◽  
pp. 68-72 ◽  
Author(s):  
Touraj Mahmoudi ◽  
Keivan Majidzadeh-A ◽  
Khatoon Karimi ◽  
Hamid Farahani ◽  
Reza Dabiri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Insulin Receptor ◽  
Case Control Study ◽  
Insulin Receptor Substrate ◽  
Protective Effects ◽  
Insulin Receptor Substrate 1 ◽  
Pcr Rflp ◽  
Obese Subjects ◽  
Control Study

Background Given the major role of obesity and insulin resistance (IR) in colorectal cancer (CRC), we investigated whether genetic variants in ghrelin ( GHRL), resistin ( RETN) and insulin receptor substrate 1 ( IRS1) were associated with CRC risk. Methods This study was conducted as a case-control study, and 750 subjects, including 438 controls and 312 patients with CRC, were enrolled and genotyped using the PCR-RFLP method. Results No significant differences were observed for GHRL (rs696217), RETN (rs3745367) and IRS1 (rs1801278, Gly972Arg or G972R) gene variants between the cases and controls. However, the IRS1 G972R R allele compared with the G allele and the G972R RR+GR genotype compared with the GG genotype appeared to be markers of decreased CRC susceptibility in the overweight/obese subjects (p = 0.024; odds ratio [OR] = 0.42, 95% confidence interval [95% CI], 0.20-0.91; and p = 0.048; OR = 0.42, 95% CI, 0.17-0.99, respectively). Furthermore, the R allele and RR+GR genotype were also associated with decreased risks for obesity in the patients with CRC (p = 0.007; OR = 0.35, 95% CI, 0.15-0.77; and p = 0.015; OR = 0.35, 95% CI, 0.15-0.72, respectively). Conclusions In accordance with previous studies, our findings suggest that the IRS1 G972R R allele and RR+GR genotype have protective effects for CRC in overweight/obese patients and for obesity in patients with CRC. Nevertheless, further studies are required to confirm these findings.

scholarly journals The Insulin Receptor Substrate 1 (Irs1) in Intestinal Epithelial Differentiation and in Colorectal Cancer

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e36190 ◽  
Author(s):  
Diana L. Esposito ◽  
Federica Aru ◽  
Rossano Lattanzio ◽  
Annalisa Morgano ◽  
Michela Abbondanza ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Insulin Receptor ◽  
Epithelial Differentiation ◽  
Insulin Receptor Substrate ◽  
Intestinal Epithelial ◽  
Insulin Receptor Substrate 1

scholarly journals Knockdown of long noncoding RNA PVT1 suppresses cell proliferation and invasion of colorectal cancer via upregulation of microRNA-214-3p

2019 ◽  
Vol 317 (2) ◽  
pp. G222-G232 ◽  
Author(s):  
An-Quan Shang ◽  
Wei-Wei Wang ◽  
Yi-Bao Yang ◽  
Chen-Zheng Gu ◽  
Ping Ji ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Insulin Receptor ◽  
Luciferase Reporter ◽  
Insulin Receptor Substrate ◽  
Insulin Receptor Substrate 1 ◽  
Gene Assay ◽  
Proliferation And Invasion ◽  
Variant Translocation ◽  
Competitive Endogenous Rna

Long noncoding RNAs (lncRNAs) have been reported to be involved in the occurrence and tumorigenesis of numerous malignant cancers. Microarray expression profiles were used to screen colorectal cancer (CRC)-related differentially expressed genes and lncRNAs, which revealed that insulin receptor substrate 1 (IRS1) and lncRNA plasmacytoma variant translocation 1 (PVT1) were highly expressed in CRC. This study aimed to investigate the regulatory role of lncRNA PVT1 in CRC. Subcellular localization detected by fluorescence in situ hybridization identified that lncRNA PVT1 was primarily located in the cytoplasm. The interaction between lncRNA PVT1 and microRNA-214-3p (miR-214-3p) and IRS1 was predicted using the RNA22 website. Next the dual luciferase reporter gene assay, RNA pull-down, and RNA immunoprecipitation assays verified lncRNA PVT1 to be a competitive endogenous RNA (ceRNA) against miR-214-3p, and IRS1 was found to be a target of miR-214-3p. The expression pattern of lncRNA PVT1, miR-214-3p, IRS1, phosphoinositide 3-kinase (PI3K), and Akt was characterized in response to lncRNA PVT1 silencing or miR-214-3p upregulation. Meanwhile, their regulatory effects on cell proliferation, invasion, and apoptosis were detected in CRC cells. With increased levels of miR-214-3p and decreased levels of lncRNA PVT1 in CRC cells, the expression of phosphatidylinositol 3-kinase, putative (PI3K) and Akt was reduced, and consequently, the cell apoptosis was stimulated and cell proliferation and invasion were suppressed. All in all, lncRNA PVT1 competitively binds to miR-214-3p to upregulate the expression of IRS1 thus activating the PI3K/Akt signaling pathway, thus accelerating CRC progression. This study suggests that lncRNA PVT1 might be a potential target of therapeutic strategies for CRC treatment. NEW & NOTEWORTHY This study mainly suggests that long noncoding (lnc)RNA plasmacytoma variant translocation 1 (PVT1) is a downregulated lncRNA in colorectal cancer (CRC), accelerating CRC progression. Strikingly, lncRNA PVT1 acts as a competitive endogenous RNA against microRNA (miR)-214-3p, whereas miR-214-3p targets insulin receptor substrate 1, which draws a comprehensive picture of the potential molecular mechanisms of lncRNA PVT1 in CRC.

scholarly journals Rapamycin Promotes Vascular Smooth Muscle Cell Differentiation through Insulin Receptor Substrate-1/Phosphatidylinositol 3-Kinase/Akt2 Feedback Signaling

2007 ◽  
Vol 282 (49) ◽  
pp. 36112-36120 ◽  
Author(s):  
Kathleen A. Martin ◽  
Bethany L. Merenick ◽  
Min Ding ◽  
Kristina M. Fetalvero ◽  
Eva M. Rzucidlo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Protein Expression ◽  
Insulin Receptor ◽  
Contractile Protein ◽  
Insulin Receptor Substrate ◽  
Phosphatidylinositol 3 Kinase ◽  
Insulin Receptor Substrate 1 ◽  
Factor I

The phenotypic plasticity of mature vascular smooth muscle cells (VSMCs) facilitates angiogenesis and wound healing, but VSCM dedifferentiation also contributes to vascular pathologies such as intimal hyperplasia. Insulin/insulin-like growth factor I (IGF-I) is unique among growth factors in promoting VSMC differentiation via preferential activation of phosphatidylinositol 3-kinase (PI3K) and Akt. We have previously reported that rapamycin promotes VSMC differentiation by inhibiting the mammalian target of rapamycin (mTOR) target S6K1. Here, we show that rapamycin activates Akt and induces contractile protein expression in human VSMC in an insulin-like growth factor I-dependent manner, by relieving S6K1-dependent negative regulation of insulin receptor substrate-1 (IRS-1). In skeletal muscle and adipocytes, rapamycin relieves mTOR/S6K1-dependent inhibitory phosphorylation of IRS-1, thus preventing IRS-1 degradation and enhancing PI3K activation. We report that this mechanism is functional in VSMCs and crucial for rapamycin-induced differentiation. Rapamycin inhibits S6K1-dependent IRS-1 serine phosphorylation, increases IRS-1 protein levels, and promotes association of tyrosine-phosphorylated IRS-1 with PI3K. A rapamycin-resistant S6K1 mutant prevents rapamycin-induced Akt activation and VSMC differentiation. Notably, we find that rapamycin selectively activates only the Akt2 isoform and that Akt2, but not Akt1, is sufficient to induce contractile protein expression. Akt2 is required for rapamycin-induced VSMC differentiation, whereas Akt1 appears to oppose contractile protein expression. The anti-restenotic effect of rapamycin in patients may be attributable to this unique pattern of PI3K effector regulation wherein anti-differentiation signals from S6K1 are inhibited, but pro-differentiation Akt2 activity is promoted through an IRS-1 feedback signaling mechanism.

scholarly journals Insulin receptor substrate 1 may play divergent roles in human colorectal cancer development and progression

2020 ◽  
Vol 26 (28) ◽  
pp. 4140-4150
Author(s):  
Karolina Lomperta ◽  
Katarzyna Jakubowska ◽  
Malgorzata Grudzinska ◽  
Luiza Kanczuga-Koda ◽  
Andrzej Wincewicz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Insulin Receptor ◽  
Cancer Development ◽  
Insulin Receptor Substrate ◽  
Human Colorectal Cancer ◽  
Insulin Receptor Substrate 1
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