MiR-1587 Regulates DNA Damage Repair and the Radiosensitivity of CRC Cells via Targeting LIG4
Ruixue Liu,
Liping Shen,
Chuxian Lin,
Junyan He,
Qi Wang,
Zhenhua Qi,
Qingtong Zhang,
Meijuan Zhou,
Zhidong Wang
Affiliations
Ruixue Liu
Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China
Liping Shen
Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China
Chuxian Lin
Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China
Junyan He
Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China
Qi Wang
Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China
Zhenhua Qi
Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China
Qingtong Zhang
Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, People’s Republic of China
Meijuan Zhou
Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, People’s Republic of China
Zhidong Wang
Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China
DNA is subject to a range of endogenous and exogenous insults that can impair DNA replication and lead to DNA double-strand breaks (DSBs). The repair capacity of cancer cells mediates their radiosensitivity, but the roles of miR-1587 during radiation resistance are poorly characterized. In this study, we explored whether miR-1587 regulates the growth and radiosensitivity of colorectal cancer (CRC) cells through its ability to regulate DNA Ligase4 (LIG4). We found that CRC cells in which miR-1587 was overexpressed inhibited cell growth and promoted apoptosis through increasing DSBs and promoting cell cycle arrest. We found that overexpression of miR-1587 significantly inhibited LIG4 messenger RNA and protein expression and further revealed the ability of miR-1587 to directly bind to the LIG4-3′-untranslated region through dual-luciferase reporter assays. More notably, miR-1587 mimics increased the radiosensitivity of CRC cells. Taken together, we show that miR-1587 overexpression enhances the formation of DSBs, arrests CRC cell growth, and enhances the radiosensivity of CRC cells through the direct repression of LIG4 expression. These results reveal novel roles for miR-1587 during DNA damage repair and the radiosensivity of CRC cells. This highlights miR-1587 as a novel therapeutic target for CRC.
