miR-206 functions as a novel cell cycle regulator and tumor suppressor in clear-cell renal cell carcinoma

Abstract

Purpose: In this study we tried to systematically investigate the tumor suppressing microRNAs in ccRCC.

Materials and methods: The MTS cell viability and colony formation assay were used to systematically detect the tumor suppressing ability of down-regulated miRNAs in ccRCC. Then miR-206 expression was detected by RT-qPCR and in situ hybridization in ccRCC cell lines and clinical samples. Oligonucleotides were used to overexpress or down-regulate miR-206. MTS cell viability, EdU cell proliferation, colony formation assay, flow cytometry, Xenograft subcutaneously and orthotopic implantations were done to examine tumor suppressing effects of miR-206 in vitro and in vivo. Luciferase assay was performed to verify the precise target of miR-206.

Results: We reviewed and experimentally analyzed the currently available miRNA expression profiles data of ccRCC and identified miR-206 as one of the most critical tumor-suppressing microRNAs in ccRCC. In addition, miR-206 inhibited ccRCC cell proliferation through inducing cell cycle arrest by directly targeting cell cycle related gene CDK4, CDK9 and CCND1.

Conclusions: All these results suggested that miR-206 functioned as a novel cell cycle regulator and tumor suppressor in ccRCC and could be considered as a potential target for ccRCC therapy.

Keywords: ccRCC; cell cycle; miR-206; tumor suppressor.