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Long noncoding RNA lnc-RI regulates DNA damage repair and radiation sensitivity of CRC cells through NHEJ pathway

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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 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.

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Acknowledgements

We wish to thank Dr. H.J. Fu (Beijing Institute of Radiation Medicine) for kindly providing the Dual-Luciferase Reporter Assay System.

Funding

This work was supported by grants from the National Natural Science Foundation of China [31770913 to Z.W.].

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Author notes

  1. Ruixue Liu and Qingtong Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China

    Ruixue Liu, Liping Shen, Junyan He, Dong Wang, Qi Wang, Zhenhua Qi & Zhidong Wang

  2. 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

    Ruixue Liu & Meijuan Zhou

  3. Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, People’s Republic of China

    Qingtong Zhang

  4. PLA Rocket Force Characteristic Medical Center, Beijing, People’s Republic of China

    Shuangjing Chen

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  1. Ruixue Liu
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Correspondence to Zhidong Wang.

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Animal experiments were approved by the ethics committee of the Animal Center of Beijing Institute of Radiation Medicine. Clinical samples have been reviewed and approved by the Ethics Committee of Liaoning Cancer Hospital (20190970).

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Liu, R., Zhang, Q., Shen, L. et al. Long noncoding RNA lnc-RI regulates DNA damage repair and radiation sensitivity of CRC cells through NHEJ pathway. Cell Biol Toxicol 36, 493–507 (2020). https://doi.org/10.1007/s10565-020-09524-6

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  • DOI: https://doi.org/10.1007/s10565-020-09524-6

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