miR-539 suppresses proliferation and induces apoptosis in renal cell carcinoma by targeting high mobility group A2

Renal cell carcinoma (RCC) is one of the most common urinary malignancies with a high rate of morbidity. MicroRNAs (miRNAs) have been shown to be critical post-transcriptional regulators in tumorigenesis. The present study aimed to investigate the effect of miRNA (miR)-539 on the proliferation and apoptosis of RCC. The expression of miR-539 and high mobility group AT-hook 2(HMGA2) were examined in clinical RCC specimens. The 786-O RCC cell line was also used and was transfected with miR-539 mimics or inhibitors. The correlation between miR-539 and HMGA2 was confirmed using a luciferase reporter assay. Cell viability and apoptosis were detected using MTT and flow cytometry assays. The protein levels of HMGA2, AKT, phosphorylated (p)-AKT, mammalian target of rapamycin (mTOR) and p-mTOR were analyzed using western blot analysis. The results revealed that miR-539 was negatively correlated with the expression of HMGA2 in clinical RCC specimens. Further experiments identified HMGA2 as a direct target of miR-539. The overexpression of miR-539 downregulated the expression of HMGA2, reduced cell proliferation and promoted cell apoptosis, whereas the knockdown of miR-539 led to the opposite results. miR-539 also suppressed the phosphorylation of AKT and mTOR, without altering the levels of total AKT and mTOR. Taken together, the results of the present study indicated that miR-539 negatively regulated the expression of HMGA2 in clinical specimens and in vitro. miR539 inhibited cell proliferation and induced apoptosis in RCC cells. This regulatory effect of miR-539 may be associated with the AKT signaling pathway. Therefore, miR-539 may be used as a biomarker for predicting the progression of RCC.