Frontiers in Pharmacology (Aug 2022)

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
https://doi.org/10.3389/fphar.2022.968223
Journal volume & issue
Vol. 13

Abstract

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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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