Oesophageal cancer is a progressive tumour with high mortality. However, therapies aimed at treating oesophageal cancer remain relatively limited. Accumulating studies have highlighted long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR), microRNA-204 (miR-204) and homeobox C8 (HOXC8) in the progression of oesophageal cancer. Herein, we tried to demonstrate the function of HOTAIR, miR-204 and HOXC8 in oesophageal cancer and their relationship. Differentially expressed genes involved in oesophageal cancer were identified. The endogenous expression of HOTAIR and miR-204 in oesophageal cancer cell lines was altered to elucidate their effects and to identify the interaction among HOTAIR, miR-204 and HOXC8. We also explored the underlying regulatory mechanisms of HOTAIR and miR-204 with siRNA against HOTAIR, miR-204 mimic or miR-204 inhibitor. Cell proliferation, migration, invasion and apoptosis were subsequently detected. Xenograft in nude mice was induced to evaluate tumourigenicity. miR-204 was down-regulated, while HOTAIR and HOXC8 were up-regulated in the oesophageal cancer tissues. HOTAIR could competitively bind to miR-204 and miR-204 could further target HOXC8. The oesophageal cancer cells treated with si-HOTAIR or miR-204 mimic exhibited decreased expression levels of HOXC8, Vimentin and MMP-9, but increased E-cadherin level. Silenced HOTAIR or elevated miR-204 inhibited proliferation, migration and invasion, along with stimulated apoptosis of oesophageal cancer cells. In summary, our results show that lncRNA HOTAIR could specifically bind to miR-204 as a competing endogenous RNA and regulate miR-204 and HOXC8. Hence, down-regulation of HOTAIR could inhibit progression of oesophageal cancer, indicating a novel target for oesophageal cancer treatment.
Keywords: HOX transcript antisense RNA; MicroRNA-204; homeobox C8; invasion; long non-coding RNA; migration; oesophageal cancer; proliferation.
© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.