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PCAT‐1 contributes to cisplatin resistance in gastric cancer through epigenetically silencing PTEN via recruiting EZH2
Author(s) -
Li Hui,
Ma Xuhui,
Yang Desheng,
Suo Zhimin,
Dai Rujiang,
Liu Chunhong
Publication year - 2020
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29370
Subject(s) - cisplatin , pten , ezh2 , cancer research , gene silencing , gene knockdown , long non coding rna , downregulation and upregulation , cancer , histone h3 , biology , histone , apoptosis , pi3k/akt/mtor pathway , gene , genetics , chemotherapy
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.