Long noncoding RNA lnc-RI regulates DNA damage repair and radiation sensitivity of CRC cells through NHEJ pathway
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ORIGINAL ARTICLE
Long noncoding RNA lnc-RI regulates DNA damage repair and radiation sensitivity of CRC cells through NHEJ pathway Ruixue Liu & Qingtong Zhang & Liping Shen & Shuangjing Chen & Junyan He & Dong Wang & Qi Wang & Zhenhua Qi & Meijuan Zhou & Zhidong Wang
Received: 15 January 2020 / Accepted: 28 March 2020 # Springer Nature B.V. 2020
Abstract A percentage of colorectal cancer (CRC) patients display low sensitivity to radiotherapy, which affects its therapeutic effect. Cancer cells DNA double-strand breaks (DSBs) repair capacity is crucial for radiosensitivity, but the roles of long noncoding RNAs (lncRNAs) in this process are largely
uncharacterized. This study aims to explore whether lnc-RI regulates CRC cell growth and radiosensitivity by regulating the nonhomologous end-joining (NHEJ) repair pathway. CRC cells in which lnc-RI has been silenced showed lower cell growth and higher apoptosis rates due to increased DSBs and cell cycle arrest. We
Ruixue Liu and Qingtong Zhang contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10565-020-09524-6) contains supplementary material, which is available to authorized users. R. Liu : L. Shen : J. He : D. Wang : Q. Wang : Z. Qi : Z. Wang (*) Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China e-mail: [email protected]
Z. Qi e-mail: [email protected] R. Liu : M. 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
R. Liu e-mail: [email protected] M. Zhou e-mail: [email protected] L. Shen e-mail: [email protected] J. He e-mail: [email protected] D. Wang e-mail: [email protected] Q. Wang e-mail: [email protected]
Q. Zhang Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, People’s Republic of China e-mail: [email protected] S. Chen PLA Rocket Force Characteristic Medical Center, Beijing, People’s Republic of China e-mail: [email protected]
Cell Biol Toxicol
found that miR-4727-5p targets both lnc-RI and LIG4 mRNA and inhibit their expression. CRC cells showed increased radiosensitivity when lnc-RI was silenced. These results reveal novel roles for lnc-RI in both DNA damage repair and radiosensitivity regulation in CRC cells. Our study revealed that lnc-RI regulates LIG4 expression through lnc-RI/miR-4727-5p/LIG4 axis and regulates NHEJ repair efficiency to participate in DNA damage repair. The level of lnc-RI was negatively correlated with the radiosensitivity of CRC cells, indicates that lnc-RI may be a potential target for CRC therapy. We also present the first report of the function of miR-4727-5p. Keywords Lnc-RI . lncRNA . Non-homologous endjoining (NHEJ) . LIG4 . miR-4727-5p
Introduction Colorectal cancer (CRC) is a predominant cancer with high incide
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