HOTAIR Promotes Cisplatin Resistance of Nasopharyngeal Carcinoma Cells by Regulating Cell Proliferation, Invasion, and Apoptosis via miR-106a-5p/SOX4 Axis

Background: Nasopharyngeal carcinoma (NPC) is a highly malignant neoplasm originating from nasopharyngeal mucosa, and the emergence of multi-drug resistance poses a huge challenge for clinical treatment of NPC. LncRNA HOTAIR (HOX antisense intergenic RNA) has been reported to be associated with many malignancies, including NPC. However, the underlying mechanisms of HOTAIR involved in drug resistance in NPC are obscure.Methods: Quantitative polymerase chain reaction (qPCR) was employed to determine the HOTAIR, miR-106a-5p and SOX4 expression in NPC tissues and cells. The target relationship between HOTAIR and miR-106a-5p or miR-106a-5p and SOX4 was determined using dual-luciferase reporter assay. Cell proliferation, apoptosis, migration and invasion were explored using Cell counting kit-8 (CCK-8), flow cytometer and Transwell assays. The protein levels were confirmed using western blot.Results: Our study showed that HOTAIR was upregulated in cisplatin (DDP)-resistant NPC tissues and cells. HOTAIR knockdown decreased the DDP resistance, drug resistance related gene expression, cell proliferation and invasion, and promoted apoptosis of C666-1/DDP and CNE2/DDP cells. Mechanism researches displayed that miR-106a-5p was down-regulated in DDP-resistant NPC tissues and cells. miR-106a-5p directly bound with HOTAIR and was regulated by HOTAIR. SOX4 was inhibited by miR-106a-5p at a posttranscriptional level, and the transfection of miR-106a-5p reversed the upregulation of SOX4 caused by HOTAIR overexpression. Increase or decrease of miR-106a-5p suppressed the effect of HOTAIR upregulation or downregulation on DDP resistance, cell proliferation, invasion and apoptosis of C666-1/DDP and CNE2/DDP cells. Moreover, the transfection of SOX4 siRNA reversed the decrease of DDP resistance, cell proliferation and invasion, and rescued the increase of apoptosis induced by miR-106a-5p inhibition. Conclusions: These data suggested that HOTAIR enhanced DDP resistance of C666-1/DDP and CNE2/DDP cells by affecting cell proliferation, invasion, and apoptosis via miR-106a-5p/SOX4 axis.