Upregulation of nuclear-enriched abundant transcript 1 confers oxaliplatin resistance to gastric cancer

核富集转录本 1 的上调使胃癌产生奥沙利铂耐药性

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作者:Yunsong Li, Chunwei Peng, Changyi Fang, Kai Huang

Abstract

The present study aims to investigate the roles of nuclear-enriched abundant transcript 1 (NEAT1) in the regulation of oxaliplatin resistance to gastric cancer (GC). Oxaliplatin-resistant cell lines were constructed using stepwise selection. NEAT1 knockdown and overexpression of NEAT1 were performed. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and colony formation assays were used to evaluate cell proliferation. Propidium iodide (PI) and annexin V staining were used to evaluate cell apoptosis. A dual-luciferase reporter assay was used to evaluate the molecular interactions. Quantitative polymerase chain reaction (qPCR) was used to determine messenger RNA (mRNA) expression. Western blotting was used to determine the protein expression. Kaplan-Meier's analysis was performed to evaluate the relationship between NEAT1 and poor prognosis in GC. NEAT1 was upregulated in oxaliplatin-resistant GC cells and associated with poor prognosis in GC patients. NEAT1 knockdown suppressed oxaliplatin resistance, whereas overexpression of NEAT1 induced oxaliplatin resistance. In addition, the expressions of NEAT1 were negatively associated with miR-26 expressions. Overexpression of NEAT1 attenuated the inhibitory effects of miR-26 on the enhancer of zeste homolog 2 (EZH2). The roles of NEAT1 in the regulation of oxaliplatin resistance to GC are in part by ameliorating the inhibitory effect of miR-26 on EZH2.

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