Downregulation of miR-1 in colorectal cancer promotes radioresistance and aggressive phenotypes
Yong Wu, Ning Pu, Wenzhao Su, Xiaodong Yang, Chungen Xing
Abstract
Background: Colorectal cancer (CRC) remains to be one of the most common malignancies worldwide. Various studies have demonstrated that microRNAs (miRs) play a critical role in regulating cancer progression and sensitivity to chemoradiotherapy. miR-1 was found to be aberrantly expressed in CRC. However, it has not been fully elucidated whether miR-1 regulated CRC cell radioresistance. Methods: The expression of miR-1 was detected using quantitative real-time polymerase chain reaction in CRC tissues and cell lines. Colony survival and proliferation were determined using colony formation assay and MTT assay, respectively. Apoptosis and levels of related proteins, Bax and Bcl-2, were detected using flow cytometer assay and western blotting analysis. Migration and invasion were measured using wound healing assay and transwell invasion assay. The levels of invasion-associated proteins, E-cadherin, MMP2 and MMP9, were detected using western blotting analysis. Results: miR-1 was found to be downregulated in CRC tissues and cell lines compared with adjacent normal tissues. In vitro, miR-1 overexpression significantly suppressed colony survival and proliferation, and induced cell apoptosis under irradiation, but no apoptosis was detected without irradiation. Furthermore, miR-1 mimics promoted the expression of Bax and E-cadherin and decreased the expression of Bcl-2, MMP2 and MMP9, and apparently impaired the invasion and migration of CRC cells in synergy with radiotherapy. Conclusion: miR-1 enhanced the radiosensitivity of CRC cells by inducing cell apoptosis and the synergic inhibition of aggressive phenotypes, which may serve as a promising therapeutic target for CRC patients.