OncoTargets and Therapy (Jun 2021)

G9a Regulates Cell Sensitivity to Radiotherapy via Histone H3 Lysine 9 Trimethylation and CCDC8 in Lung Cancer

  • Li Y,
  • Chen Z,
  • Cao K,
  • Zhang L,
  • Ma Y,
  • Yu S,
  • Jin H,
  • Liu X,
  • Li W

Journal volume & issue
Vol. Volume 14
pp. 3721 – 3728

Abstract

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Yunfen Li,1– 4,* Zhengting Chen,1,* Ke Cao,1,* Lan Zhang,1,* Yuhui Ma,1 Shuhui Yu,1 Hanyu Jin,1 Xiaoling Liu,1 Wenhui Li1 1Department of Radiotherapy, Third Affiliated Hospital of Kunming Medical, Yunnan Cancer Hospital, Kunming City, Yunnan Province, People’s Republic of China; 2Department of Oncology, Yunnan Boya Hospital, Kunming City, Yunnan Province, People’s Republic of China; 3College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu City, Sichuan Province, People’s Republic of China; 4Department of Medicine, Lizhu Pharmaceutical Group Co., Ltd., Zhuhai City, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenhui LiDepartment of Radiotherapy, Third Affiliated Hospital of Kunming Medical, Yunnan Cancer Hospital, No.519 Kunzhou Road, Kunming City, Yunnan Province, People’s Republic of ChinaEmail [email protected]: To investigate the role and underlying mechanism of G9a and CCDC8 in lung cancer radioresistance.Methods: Western blotting assays were used for G9a, CCDC8, H3K9me3 expression detection. MTT assays and clone formation assays were used for measuring cell proliferation activities. Flow cytometry assays were used for cell apoptosis detection. The enrichment of H3K9me3 in CCDC8 promoter was measured by chromatin immunoprecipitation assay.Results: G9a and G9a-mediated H3K9me3 are upregulated in radioresistant lung cancer cells (A549/IR cell and XWLC-05/IR cell). Blocking G9a not only promotes radiosensitivity of A549/IR cell and XWLC-05/IR cell but also reduces aggressive behavior of radioresistant A549 cell/IR and XWLC-05/IR cell. In addition, G9a-controlled H3K9me3 is able to binding to the promoter of tumor suppressor gene CCDC8 and suppresses CCDC8 expression. CCDC8 dysregulation is responsible for G9a-mediated radioresistance of A549/IR cell and XWLC-05/IR cell.Conclusion: G9a and H3K9me3 contribute to the lung cancer radioresistance via modulating CCDC8 expression.Keywords: radiotherapy, lung cancer, G9a, H3K9me3, CCDC8

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