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

G9a 通过组蛋白 H3 赖氨酸 9 三甲基化和 CCDC8 调节肺癌细胞对放射治疗的敏感性

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作者:Yunfen Li #, Zhengting Chen #, Ke Cao #, Lan Zhang #, Yuhui Ma, Shuhui Yu, Hanyu Jin, Xiaoling Liu, Wenhui Li

Conclusion

G9a and H3K9me3 contribute to the lung cancer radioresistance via modulating CCDC8 expression.

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.

Purpose

To investigate the role and underlying mechanism of G9a and CCDC8 in lung cancer radioresistance.

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.

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