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

Cheng Zhang; Tong Kang; Xinyi Wang; Jizhao Wang; Lin Liu; Jiawei Zhang; Xu Liu; Rong Li; Jiansheng Wang; Jia Zhang

doi:10.3389/fphar.2022.968223

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

Front Pharmacol. 2022 Aug 25:13:968223. doi: 10.3389/fphar.2022.968223. eCollection 2022.

Authors

Cheng Zhang¹, Tong Kang², Xinyi Wang¹, Jizhao Wang¹, Lin Liu¹, Jiawei Zhang¹, Xu Liu¹, Rong Li³, Jiansheng Wang¹, Jia Zhang¹

Affiliations

¹ Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
² Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
³ Department of Radiotherapy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

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.

Keywords: Atg5; DDP-resistance; LINC-PINT; autophagy; gastric cancer.