miR-106a* inhibits the proliferation of renal carcinoma cells by targeting IRS-2

Abstract

MicroRNAs play critical roles in the development and progression of human cancers. Although it has been reported that miR-106a* is downregulated in follicular lymphoma, its role in renal cell carcinoma (RCC) remains unknown. This study investigated the expression and role of miR-106a* in human RCC. Our results showed that the miR-106a* expression decreased dramatically in clinical RCC tissues and cell lines. In vitro, overexpression of miR-106a* suppressed RCC cell proliferation and S/G2 transition, whereas inhibition of miR-106a* promoted cell proliferation and S/G2 transition. It was also found that miR-106a* expression was inversely correlated with the expression of insulin receptor substrate 2 (IRS-2). IRS-2 was determined to be a direct target of miR-106a* by a luciferase reporter assay. Importantly, silencing IRS-2 resulted in the same biologic effects as those of miR-106a* overexpression in RCC cells, including inhibition of RCC cell proliferation and triggering of S/G2 cell cycle arrest with inhibition of the PI3K/Akt signaling pathway. These results indicate that miR-106a* affects RCC progression by targeting IRS-2 with suppression of the PI3K/Akt signaling pathway in RCC cells. The findings suggest miR-106a* as a novel strategy for RCC treatment.

Keywords: Insulin receptor substrates 2; PI3K/Akt signaling pathway; Proliferation; Renal cell carcinoma; miR-106a*.