Knockdown of lncRNA NEAT1 suppresses hypoxia-induced migration, invasion and glycolysis in anaplastic thyroid carcinoma cells through regulation of miR-206 and miR-599

Abstract

Abstract Background Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal malignancies. Long non-coding RNAs (lncRNAs) are being found to play crucial roles in ATC progression. Herein, we focused on the role of nuclear paraspeckle assembly transcript 1 (NEAT1) on ATC progression under hypoxia and underlying mechanisms governing it. Methods The expression levels of NEAT1, miR-206 and miR-599 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell migration and invasion abilities were detected using transwell assays. Glucose consumption and lactate production were determined using a corresponding commercial assay kit. Western blot was performed to evaluate the level of hexokinase 2 (HK2). The targeted interplays between NEAT1 and miR-206 or miR-599 were confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft model was established to observe the effect of NEAT1 on tumor growth in vivo. Results Our data indicated that NEAT1 was highly expressed in ATC tissues and cells, and hypoxia induced NEAT1 expression in ATC cells. NEAT1 depletion repressed ATC cell migration, invasion and glycolysis under hypoxia. Mechanistically, NEAT1 acted as a molecular sponge of miR-206 and miR-599. Moreover, the repressive effects of NEAT1 knockdown on ATC cell migration, invasion and glycolysis under hypoxia were mediated by miR-206 or miR-599. Additionally, NEAT1 knockdown weakened tumor growth in vivo. Conclusion In conclusion, our study suggested that a low NEAT1 expression suppressed the migration, invasion, and glycolysis in ATC cells under hypoxia at least partially through modulating miR-206 and miR-599, providing new therapeutic strategies for ATC treatment.