Silencing of HIF-1 alpha inhibited the expression of lncRNA NEAT1 to suppress development of hepatocellular carcinoma under hypoxia
Silencing of HIF-1 alpha inhibited the expression of lncRNA NEAT1 to suppress development of hepatocellular carcinoma under hypoxia
复制标题
沉默HIF-1α抑制lncRNA NEAT1的表达抑制缺氧条件下肝细胞癌的发展
DOI：
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发表时间：
2020
影响因子：
2.2
通讯作者：
Shen Wenrong
中科院分区：
文献类型：
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作者：
Zhang Xiuming;Kang Zheng;Xie Xiaodong;Qiao Wei;Zhang Lei;Gong Zhen;Chen Yan;Shen Wenrong
背景：我们旨在探讨缺氧诱导因子-1 α (HIF-1 α)与lncRNA核富集丰富转录物1 （NEAT1）的关系及其在缺氧条件下肝细胞癌（HCC）中的功能。方法：采用qRT-PCR检测HCC组织及相应非肿瘤组织中HIF-1 α和NEAT1水平，并采用Pearson检验分析其在HCC组织中的相关性。采用log-rank检验检测HCC患者总生存率与HIF-1 α和NEAT1基因的关系。收集HCC患者NEAT1的临床病理特征。采用qRT-PCR和Western blot检测HCC细胞中HIF-1 α和NEAT1的水平，并采用共免疫沉淀（Co-IP）法检测它们之间的关系。CCK-8法检测细胞活力、划痕愈合和transwell法检测细胞迁移和侵袭。NEAT1与HIF-1 α在裸鼠肿瘤发生过程中的相互作用通过异种移植肿瘤实验确定。结果：NEAT1与HIF-1 α在HCC组织中高表达并呈正相关，且NEAT1高表达与HCC患者TNM分期及转移呈正相关。肝癌患者NEAT1或HIF-1 α上调预后较差。NEAT1被HIF-1 α诱导，被siHIF-1 α抑制。NEAT1过表达进一步促进缺氧条件下HCC的发展，同时促进细胞活力、迁移和侵袭，抑制细胞凋亡，这种作用可通过下调HIF-1 α而逆转。NEAT1过表达可促进肿瘤生长，而下调HIF-1 α可逆转这一过程。结论：HIF-1 α下调可抑制NEAT1的表达，抑制HCC的进展，改善其预后。
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.