Methylation of TMEM176A, a key ERK signaling regulator, is a novel synthetic lethality marker of ATM inhibitors in human lung cancer

TMEM176A 甲基化是 ERK 信号调节剂的关键,也是人类肺癌中 ATM 抑制剂的新型合成致死标记

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作者:Hongxia Li, Weili Yang, Meiying Zhang, Tao He, Fuyou Zhou, James G Herman, Liming Hu, Mingzhou Guo

Aim

The role of TMEM176A methylation in lung cancer and its therapeutic application remains unclear. Materials and

Conclusion

The expression of TMEM176A is regulated by promoter region methylation. Methylation of TMEM176A is a potential lung cancer diagnostic marker and a novel synthetic lethal therapeutic marker for AZD0156.

Methods

Nine lung cancer cell lines and 123 cases of cancer tissue samples were employed.

Results

TMEM176A was methylated in 53.66% of primary lung cancer. Restoration of TMEM176A expression induced cell apoptosis and G2/M phase arrest, and inhibited colony formation, cell proliferation, migration and invasion. TMEM176A suppressed H1299 cell xenograft growth in mice. Methylation of TMEM176A activated ERK signaling and sensitized H1299 and H23 cells to AZD0156, an ATM inhibitor.

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