Long noncoding RNA HOTAIR promotes cisplatin resistance in gastric cancer through promoting WIF-1 promoter methylation

Background and objective: Increasing evidence has illustrated that long noncoding RNAs (lncRNAs) could function as oncogenes and tumor suppressors in human carcinogenesis. However, the roles of lncRNAs in chemoresistance of human gastric cancer (GC) remain largely undefined. The current study aimed to verify the correlation between lncRNA HOTAIR expression and cisplatin resistance of GC. Methods: Cisplatin-resistant BGC823/DDP cells were established from the parental GC BGC823 cells. The expression levels of HOTAIR and WIF-1 mRNA in cells were investigated via qRT-PCR, and WIF-1 protein expression was detected by western blot analysis. CCK-8 assay was performed to explore the cell viability of the BGC823 and BGC823/DDP GC cells to cisplatin. The apoptotic rates to cisplatin of the GC cell lines were investigated via a flow cytometer, and the wound healing assay was conducted to assess the cell mobility to cisplatin of the GC cells. Results: In BGC823/DDP cells, HOTAIR expression were greatly up-regulated, while the WIF-1 promoter methylation level was significant increased and the mRNA and protein expression levels of WIF-1 were obviously reduced (all P<0.05). Silence of HOTAIR significantly suppressed WIF-1 promoter methylation and up-regulated WIF-1 expressions both at mRNA and protein levels (all P<0.05). The IC50 value of cisplatin in BGC823/DDP cells, remarkably higher compared to that of BGC823 cells (all P<0.05), could be dramatically down-regulated by silence of HOTAIR (all P<0.05). The apoptotic rate to cisplatin of BGC823/ DDP cells was significantly down-regulated, while the cell mobility to cisplatin of BGC823/DDP cells was remarkably suppressed than that of BGC823 cells (all P<0.05); down-regulation of HOTAIR obviously facilitated the apoptosis of BGC823/DDP cells and inhibited the cell mobility to cisplatin (P<0.05). Conclusions: Our results shed novel light on the roles of HOTAIR/WIF-1 signaling axis in cisplatin resistance, and HOTAIR might be considered as a potential therapeutic approach to reverse the cisplatin resistance in GC.