Knockdown of lncRNA XIST inhibits hypoxia-induced glycolysis, migration and invasion through regulating miR-381-3p/NEK5 axis in nasopharyngeal carcinoma

OBJECTIVE: Hypoxia is an important feature of nasopharyngeal carcinoma (NPC). Growing evidence demonstrated that long non-coding RNAs (lncRNAs) could participate in cancer progression and hypoxia regulation. However, the exact roles and underlying mechanism of lncRNA X-inactive specific transcript (XIST) in NPC under hypoxia are still unclear. MATERIALS AND METHODS: The expressions of XIST, microRNA-381-3p (miR-381-3p) and NIMA related kinase 5 (NEK5) were detected by quantitative Real-time polymerase chain reaction (qRT- PCR). The glucose consumption and lactate production were measured using the glucose assay kit and lactate assay kit, respectively. Western blot assay was used to determine the protein levels of hexokinase II (HK2) and NEK5. Transwell assay was employed to evaluate cell migration and invasion. The interaction between miR-381-3p and XIST or NEK5 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay. The mice xenograft model was established to investigate the roles of XIST in NPC progression in vivo. RESULTS: XIST and NEK5 were highly expressed while miR-381-3p was lowly expressed in NPC (tissues and cells) and hypoxia-induced NPC cells. Deficiency of XIST or NEK5 suppressed hypoxia-induced glycolysis and metastasis in NPC cells. Moreover, miR-381-3p could directly bind to XIST and its inhibition reversed the inhibitory effects of XIST knockdown on glycolysis and metastasis under hypoxia. NEK5 was a direct target of miR-381-3p and its interference attenuated the promotive effects of miR- 381- 3p downregulation on glycolysis and metastasis under hypoxic conditions. Besides, interference of XIST decreased tumor growth by upregulating miR-381-3p and downregulating NEK5. CONCLUSIONS: XIST knockdown inhibited glycolysis and metastasis in hypoxia-induced NPC cells through regulating miR-381-3p/NEK5 axis, providing new insights into the pathogen- esis of NPC.