microRNA-16-5p enhances radiosensitivity through modulating cyclin D1/E1–pRb–E2F1 pathway in prostate cancer cells

Background: Prostate cancer (CaP) was the second most common cancer in men worldwide in 2012, and radiation therapy is one of the most common definitive treatment options for localized CaP. However, radioresistance is a major challenge for current radiotherapy, accumulating evidence suggests microRNAs (miRNAs), as an important regulator in cellular ionizing radiation (IR) responses, are closely correlated with radiosensitivity in many cancers. Methods: We performed human miRNA probe hybridization chip analysis to identify the expression profile of miRNAs in CaP cells exposed to IR, and then we analysed the cell proliferation, cell viability, and cell cycle after transfection of miR-16-5p into the CaP cells. Analysis of the cyclin D1/E1–pRb–E2F1 pathway related proteins were performed by western blotting. Results: microRNA- 16-5p (miR-16-5p) is significantly upregulated in CaP LNCaP cells following IR and can enhance radiosensitivity through modulating the cyclin D1/E1–pRb–E2F1 pathway. Overexpression of miR-16-5p suppressed cell proliferation, reduced cell viability, and induced cell cycle arrest at G0/G1 phase, resulting in enhanced radiosensitivity in LNCaP cells. Additionally, miR-16-5p specifically targeted the cyclin D1/E1-3′-UTR in LNCaP cells and affected the expression of cyclin D1/E1 at both mRNA and protein levels. Conclusions: miR-16-5p enhanced radiosensitivity of CaP cells, the mechanism may be through modulating the cyclin D1/cyclin E1/pRb/E2F1 pathway to cause cell cycle arrest at G0/G1 phase. These findings provided new insight into the correlation between miR-16-5p, cell cycle arrest, and radiosensitivity in CaP, revealed a previously unrecognized function of miR-16-5p–cyclin D1/E1–pRb–E2F1 regulation in response to IR and may offer an alternative therapy to improve the efficiency of conventional radiotherapy. Legal entity responsible for the study: Institute of Modern Physics, Chinese Academy of Sciences. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.