Silencing of HIF-1α inhibited the expression of lncRNA NEAT1 to suppress development of hepatocellular carcinoma under hypoxia

Background: We aimed to explore the relationship between hypoxia-inducible factors-1 alpha (HIF-1 alpha) and lncRNA nuclear-enriched abundant transcript 1 (NEAT1), and their functions on hepatocellular carcinoma (HCC) under hypoxia. Methods: HIF-1 alpha and NEAT1 levels in HCC tissues and corresponding non-tumor tissues were determined by qRT-PCR, and the correlations of their levels in HCC tissues were analyzed by Pearson test. The relationship between overall survival and the two genes (HIF-1 alpha and NEAT1) for HCC patients was detected by log-rank test. Clinicopathological features of NEAT1 in HCC patients were collected. HIF-1 alpha and NEAT1 levels in HCC cells were measured by qRT-PCR and Western blot, and their relationship was determined by co-immunoprecipitation (Co-IP) assay. Cell viability, migration and invasion were detected by CCK-8, scratch wound healing and transwell assay, respectively. The interaction of NEAT1 with HIF-1 alpha in tumor development was determined by xenograft tumor assays in nude mice. Results: NEAT1 and HIF-1 alpha were highly expressed and showed a positive relationship in HCC tissues, and specifically, higher NEAT1 expression was positively associated with advanced TNM stage and metastasis in HCC patients. Up-regulated NEAT1 or HIF-1 alpha in HCC patients had poorer prognosis. NEAT1 was induced by HIF-1 alpha and suppressed by siHIF-1 alpha. NEAT1 overexpression further promoted development of HCC under hypoxia while promoting cell viability, migration and invasion and suppressing apoptosis, and such effects were reversed by down-regulating HIF-1 alpha. NEAT1 overexpression promoted tumor growth, which was reversed by down-regulating HIF-1 alpha. Conclusion: HIF-1 alpha knockdown inhibits NEAT1 expression, which suppresses progression of HCC and improves its prognosis.