miR-122 promotes proliferation and invasion of clear cell renal cell carcinoma by suppressing Forkhead box O3

Abstract

MicroRNAs (miRNAs) serve an important role in renal cancer, but renal cancer miRNA expression data remains inconsistent. Therefore, there is a requirement for integrated analysis of these data. An increasing number of studies demonstrate that miR-122 is dysregulated in numerous cancer types, including liver, lung and breast cancer, yet its role in clear cell renal cell carcinoma (ccRCC) remains unclear. In the present study, an integrated analysis of four ccRCC miRNAs expression datasets was performed and the expression of miR-122 in the present cohort was validated. The effects of cell proliferation, colony formation, migration and invasion of ccRCC cells in vitro were assayed following transfection with miR-122 mimics and inhibitor. The target gene of miR-122 was confirmed using a luciferase reporter assay, and a xenograft mouse model was used to determine the effect of miR-122 in ccRCC tumorigenicity invivo. The present results demonstrated that patients with ccRCC with an increased miR-122 level in tumor tissues had a shortened metastasis-free survival time as indicated by The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma dataset and the present ccRCC cohort. Overexpression of miR-122 in 786-O cells improved cell proliferation, colony formation, migration and invasion, while knockdown of miR-122 in SN12-PM6 cells inhibited cell growth, colony formation, migration and invasion. Western blot analysis and luciferase reporter assays were used to identify FOXO3 as a direct target of miR-122. The present results indicate that miR-122 serves a tumor-promoting role by direct targeting FOXO3 in ccRCC.