Knockdown of long non-coding RNA HOTAIR inhibits cisplatin resistance of gastric cancer cells through inhibiting the PI3K/Akt and Wnt/β-catenin signaling pathways by up-regulating miR-34a.

HOX transcript antisense RNA (HOTAIR), a well-known long non-coding RNA (lncRNA), has been reported to be related to cisplatin (DDP) resistance in gastric cancers. However, the molecular mechanism of HOTAIR in DDP resistance of gastric cancer (GC) remains largely undefined. The aim of this study was to investigate the role and underlying mechanism of HOTAIR in regulating cisplatin resistance of GC. The results showed that HOTAIR was over-expressed in GC tissues and GC cell lines, while miR-34a was low-expressed. Luciferase reporter assay and RIP assay proved that HOTAIR directly bound to miR-34a. MiR-34a expression was significantly increased in si-HOTAIR-transfected cells. Anti-miR-34a reversed the effect of si-HOTAIR on the DDP resistance, apoptosis-related genes, PI3K/Akt and Wnt/β-catenin signaling pathways in DDP-resistant GC cells, indicating that the effects of HOTAIR are dependent on miR-34a. In addition, knockdown of HOTAIR enhanced DDP inhibitory effect on tumor growth in vivo. In conclusion, HOTAIR knockdown inhibited DDP resistance of gastric cancer cells by upregulating miR-34a. The effect of HOTAIR/miR-34a axis on GC cells may be involved in the PI3K/Akt and Wnt/β-catenin signaling pathways. The results indicated that HOTAIR might be a new potential target in GC therapy.