Original article
PCAT-1 contributes to cisplatin resistance in gastric cancer through miR-128/ZEB1 axis

https://doi.org/10.1016/j.biopha.2019.109255Get rights and content
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Highlights

  • PCAT-1 was up-regulated in cisplatin-resistant gastric cancer tissues and cells.

  • Knockdown of PCAT-1 re-sensitized cisplatin-resistant gastric cancer cells to cisplatin.

  • Our study first demonstrated a ceRNA regulatory mechanism among PCAT-1, miR-128 and ZEB1 existed in gastric cancer.

  • PCAT-1/miR-128/ZEB1 axis contributed to cisplatin resistance in gastric cancer.

Abstract

Increasing evidence suggests that dysregulation of long non-coding RNAs (lncRNAs) is implicated with chemoresistance in cancers. However, their function and molecular mechanisms in gastric cancer (GC) chemoresistance remain not well elucidated. In this study, we aimed to investigate the functional role and the underlying molecular mechanism of lncRNA prostate cancer-associated transcript 1 (PCAT-1) in cisplatin (DDP) resistance of GC. Our results revealed that PCAT-1 was up-regulated in DDP-resistant GC tissues and cells. GC patients with high PCAT-1 expression levels had a poor prognosis. Knockdown of PCAT-1 facilitated the sensitivity of DDP-resistant GC cells to DDP. Additionally, PCAT-1 functioned as a sponge of miR-128 in GC cells. Moreover, inhibition of miR-128 reversed the inductive effect of PCAT-1 knockdown on DDP sensitivity of GC cells. In addition, ZEB1 was identified as a target of miR-128, and overexpression of ZEB1 could block the inductive effect of PCAT-1 knockdown on DDP sensitivity of GC cells. Besides, PCAT-1 knockdown enhanced DDP sensitivity in tumors in vivo. In summary, PCAT-1 confers DDP resistance in GC cells through miR-128/ZEB1 axis, providing a promising therapeutic strategy for GC.

Keywords

lncRNA PCAT-1
Gastric cancer
Cisplatin
miR-128
ZEB1

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