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microRNA‐16‐5p enhances radiosensitivity through modulating Cyclin D1/E1–pRb–E2F1 pathway in prostate cancer cells
Author(s) -
Wang Fang,
Mao Aihong,
Tang Jinzhou,
Zhang Qianjing,
Yan Junfang,
Wang Yupei,
Di Cuixia,
Gan Lu,
Sun Chao,
Zhang Hong
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27989
Subject(s) - radiosensitivity , lncap , cell cycle , cancer research , cyclin d1 , radioresistance , microrna , biology , cyclin e1 , cell cycle checkpoint , cancer cell , cancer , cell culture , medicine , radiation therapy , biochemistry , genetics , gene
Prostate cancer (CaP) is 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 the current radiotherapy, accumulating evidences suggest microRNAs (miRNAs), as an important regulator in cellular ionizing radiation (IR) responses, are closely correlated with radiosensitivity in many cancers. Here, we identified microRNA‐16‐5p(miR‐16‐5p) is significantly upregulated in CaP LNCaP cells following IR and can enhance radiosensitivity through modulating Cyclin D1/E1–pRb–E2F1 pathway. To identify the expression profile of miRNAs in CaP cells exposed to IR, we performed human miRNA probe hybridization chip analysis and miR‐16‐5p was found to be significantly overexpressed in all treatment groups that irradiated with different doses of X‐rays and heavy ions ( 12 C 6+ ). Furthermore, 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 in both mRNA and protein levels. Taken together, miR‐16‐5p enhanced radiosensitivity of CaP cells, the mechanism may be through modulating 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.