The aim of this study was to investigate the functional role and the underlying molecular mechanism of long noncoding RNA (lncRNA) prostate cancer-associated transcript 1 (PCAT-1) in cisplatin resistance of gastric cancer (GC). Our results indicated that PCAT-1 was overexpressed in CDDP-resistant GC tumor tissues and cell lines. High expression of PCAT-1 was closely correlated with short overall survival in patients with GC. Downregulation of PCAT-1 resensitized CDDP-resistant GC cells to cisplatin. In addition, PCAT-1 epigenetically silenced PTEN through binding to the histone methyltransferase enhancer of zeste homolog 2 (EZH2), thus increasing H3K27me3. More importantly, PTEN silencing counteracted PCAT-1 knockdown-mediated enhancement in cisplatin sensitivity of CDDP-resistant GC cells. In summary, PCAT-1 led to cisplatin resistance in GC cells through epigenetically suppressing PTEN expression, providing a novel therapeutic strategy for GC patients with chemoresistance.
Journal of cellular biochemistry. 2019 Sep 03 [Epub ahead of print]
Hui Li, Xuhui Ma, Desheng Yang, Zhimin Suo, Rujiang Dai, Chunhong Liu
Department of Digestion, Huaihe Hospital of Henan University, Kaifeng, China.