MiR-143 and MiR-145 Regulate IGF1R to Suppress Cell Proliferation in Colorectal Cancer

Abstract

Insulin-like growth factor 1 receptor (IGF1R) is a transmembrane receptor that is activated by insulin-like growth factor 1 (IGF-1) and by a related hormone called IGF-2. It belongs to the large class of tyrosine kinase receptors and plays an important role in colorectal cancer etiology and progression. In this study, we used bioinformatic analyses to search for miRNAs that potentially target IGF1R. We identified specific target sites for miR-143 and miR-145 (miR-143/145) in the 3′-untranslated region (3′-UTR) of the IGF1R gene. These miRNAs are members of a cluster of miRNAs that have been reported to exhibit tumor suppressor activity. Consistent with the bioinformatic analyses, we identified an inverse correlation between miR-143/145 levels and IGF1R protein levels in colorectal cancer tissues. By overexpressing miR-143/145 in Caco2, HT29 and SW480 colorectal cancer cells, we experimentally validated that miR-143/145 directly recognizes the 3′-UTR of the IGF1R transcript and regulates IGF1R expression. Furthermore, the biological consequences of the targeting of IGF1R by miR-143/145 were examined by cell proliferation assays in vitro. We demonstrated that the repression of IGF1R by miR-143/145 suppressed the proliferation of Caco2 cells. Taken together, our findings provide evidence for a role of the miR-143/145 cluster as a tumor suppressor in colorectal cancer through the inhibition of IGF1R translation.

microRNA-143/145 loss induces Ras signaling to promote aggressive Pten-deficient basal-like breast cancer

“…miR-143 and miR-145 target a large number of genes in various biological contexts including K-RAS and N-RAS (40,(45)(46)(47)(48)(49)(50)(51)(52)(53). To determine the mechanism through which miR-143/145 loss cooperates with pten deficiency to promote aggressive mammary tumors we performed the following analysis.…”

Efficacy of Plasma microRNA-143 and microRNA-550a as Potential Diagnostic and Prognostic Biomarkers for Chronic Hepatitis and Hepatocellular Carcinoma in Egyptian Patients

“…Discussion miR-143 is located in the chromosome 5 with a mature length of 22 [10]. A previous study has revealed that miR-143 exhibited down-regulation in many cancers such as colorectal cancer [11], pancreatic cancer [12] and lung cancer [13] in which miR-143 acts as a tumor suppressor inhibiting cell proliferation and inducing tumor cell apoptosis thus hindering the development of cancer [10]. miR-143 was exploited in many cancers e.g.…”

“…lung cancer [14], gastric cancer [15], colorectal cancer [16], osteosarcoma [17], T-cell leukemia [18] and prostate cancer [19]. While some proposed the idea of a cancer suppression effect through mediators as IGF1 [11], matrix metalloprotease 13 [17] while others proposed the effect of miR-143 on ERK5 pathway increasing apoptosis [18,19] In the present study we found no correlation between miR-143 expression and occurrence of HCC in HCV infected patients, and this was in contrary to a recent study which showed that miR-143 was down-regulated in HCC patients [1].…”

MicroRNA-182 suppresses clear cell renal cell carcinoma migration and invasion by targeting IGF1R

“…Additionally, IGF1R has been regarded as a valuable therapeutic target, and IGF1R-antagonistic monoclonal antibodies have been raised against the activity of IGF1R [32]. Several miRNAs, such as miR-133, miR-143, miR-145, and miR-503 [33][34][35], have been shown the ability to target IGF1R gene expression in different tumors. Our results also found that IGF1R was a direct target of miR-182 by luciferase reporter assay, and IGF1R could be negatively regulated by miR-182.…”