Hsa-miR-6165 downregulates insulin-like growth factor-1 receptor (IGF-1R) expression and enhances apoptosis in SW480 cells

Abstract

AbstractMicroRNAs are small non-coding RNAs that are implicated in various biological processes.Hsa-miR-6165(miR-6165), located in thep75NTRgene, is known to induce apoptosis in human cell lines, but its mechanism of action is not fully understood yet. Here, we predicted the insulin-like growth factor 1 receptor (IGF-1R) gene as abona fidetarget for miR-6165. The overexpression of miR-6165 in SW480 cells resulted in significant downregulation of IGF-1R expression as detected by real time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Also, it resulted in reduced transcript levels ofAKT2,AKT3,PI3KR3,PI3KR5,CCND1,c-MYCandP21genes detected by RT-qPCR analysis. In addition, a direct interaction between miR-6165 and a 3′UTR sequence of theIGF-1Rgene was verified through a dual luciferase assay. Furthermore,miR-6165andIGF-1Rshowed opposite patterns of expression during the neural differentiation process of NT2 cells. Annexin V analysis and MTT assay showed that miR-6165 overexpression was followed by increased apoptosis and reduced the viability rate of SW480 cells. Moreover, a lower expression level of miR-6165 was detected in high-grade colorectal tumors compared with low-grade tumors. Taken together, the results of our study suggest a tumor suppressive role of miR-6165 in colorectal cancer, which seems to take place by regulatingIGF-1Rgene expression.