LINC-PINT suppresses cisplatin resistance in gastric cancer by inhibiting autophagy activation via epigenetic silencing of ATG5 by EZH2

LINC-PINT 通过 EZH2 表观遗传沉默 ATG5 来抑制自噬激活,从而抑制胃癌的顺铂耐药性

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作者:Cheng Zhang, Tong Kang, Xinyi Wang, Jizhao Wang, Lin Liu, Jiawei Zhang, Xu Liu, Rong Li, Jiansheng Wang, Jia Zhang

Abstract

Resistance to cisplatin (DDP) is a major obstacle in the clinical treatment of advanced gastric cancer (GC). Long noncoding RNA (lncRNA) play a significant regulatory role in the development and drug resistance of GC. In this study, we reported that the lncRNA LINC-PINT was downregulated in DDP-resistant GC cells. Functional studies showed that LINC-PINT inhibited proliferation and migration of DDP-resistant GC cells in vitro, and overexpression of LINC-PINT could enhance the sensitivity of DDP-resistant GC cells to DDP. Further investigation revealed that LINC-PINT recruited enhancer of zeste homolog 2 (EZH2) to the promotor of ATG5 to inhibit its transcription, leading to the suppression of autophagy and DDP resensitization. Collectively, our results revealed how the LINC-PINT/EZH2/ATG5 axis regulates autophagy and DDP resistance in GC. These data suggest that LINC-PINT may be a potential therapeutic target in GC.

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