Downregulation of microRNA-15a suppresses the proliferation and invasion of renal cell carcinoma via direct targeting of eIF4E

The downregulation of microRNA-15a has been reported in several human tumors. However, its expression and functional importance in renal cell carcinoma (RCC) remain unknown. The aim of the present study was to investigate its expression, biological functions and underlying mechanisms in RCC tumorigenesis. The expression levels of miR-15a were examined by qRT-PCR in 40 RCC specimens and adjacent-paired normal tissues. Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry and Transwell assays were used to explore the potential influence of miR-15a transfection on RCC cell proliferation, the cell cycle, cell apoptosis, and cell invasion. Luciferase reporter assays were performed to confirm the potential target of miR-15a, in combination with qRT-PCR, western blotting and immunohistochemical assays. We found that miR-15a was significantly downregulated in most RCC specimens compared with adjacent normal tissues (P<0.01). Overexpression of miR-15a inhibited cellular growth, suppressed invasion and arrested cells at the G1/G0 phase, and induced cell apoptosis in RCC cells. Luciferase assays revealed that miR-15a directly targeted the binding site of the 3′-untranslated region (3′-UTR) of eIF4E, and inhibited its expression at both mRNA and protein levels. eIF4E expression was negatively associated with miR-15a expression in RCC tissues. eIF4E overexpression treatment partially abrogated the inhibitory effect of miR-15a on cell proliferation and invasion, as well as inactivated P13K/AKT/mTOR signaling in RCC cells. In conclusion, the present study indicated that miR-15a downregulation was associated with cell proliferation and invasion by directly targeting eIF4E during RCC progression. Thus, it may serve as a potential tumor suppressor and therapeutic target for the treatment of RCC.