Long non-coding RNA ZNF674-AS1 antagonizes oxaliplatin resistance of gastric cancer via regulating EZH2-mediated methylation of CHST7

Chemoresistance leads the cause of poor outcome of patients with gastric cancer (GC). Long non-coding RNAs (LncRNAs) is intimately involved in the regulation of tumorigenesis and progression. Here, we demonstrated ZNF674-AS1 was down-regulated in oxaliplatin (OXA)-resistant tissues and cell lines, lower level of ZNF674-AS1 predicted poor prognosis of GC patients. Besides, forced expression of ZNF674-AS1 not only reduced cell viability, colony formation, expression of drug-resistant markers but also promoted cell apoptosis of OXA-resistant GC cells, exposed to oxaliplatin. Silence of ZNF674-AS1 exhibited an opposite effects on OXA resistance of GC cells. Further mechanistic research showed that ZNF674-AS1 interacted with EZH2, led to higher methylation level of target gene CHST7. In addition, functional experiments verified that depletion of CHST7 re-sensitized OXA-resistant GC cells to OXA. Thus, our results indicated that ZNF674-AS1 suppressed OXA resistance of GC through EZH2-mediated inhibition of CHST7, providing potential theoretic basis and therapeutic strategy for chemoresistant GC.