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

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.