School of Clinical Medicine, Hubei University of Science and Technology, Xianning, China.
Department of Infection, The Second Affiliated Hospital of Hubei University of Science and Technology, Xianning, China.
Cell Biol Int. 2021 Nov;45(11):2275-2286. doi: 10.1002/cbin.11675. Epub 2021 Aug 3.
Hypoxia promotes the progression of hepatocellular carcinoma. However, the hypoxia regulatory network in hepatocellular carcinoma is known to be limited. Thus, this study aimed to identify the crucial hypoxia-associated genes and to explore their effects and molecular mechanisms in hepatocellular carcinoma cells. FUT11 was first identified as a crucial hypoxia-associated gene through bioinformatics analysis. High FUT11 mRNA levels were positively correlated with poor clinical parameters. FUT11 knockdown under normoxia and hypoxia both decreased hepatocellular carcinoma cell proliferation, colony formation, migration, and invasion. HIF1α binds to the promoter of FUT11 and increases its transcription and co-expression with FUT11 in hepatocellular carcinoma tissues. Overexpression of FUT11 in HIF1α knockdown cells reversed the inhibitory effects of HIF1α suppression on hepatocellular carcinoma cell proliferation and mobility under hypoxia. Therefore, our findings indicate that FUT11 is a key target gene of HIF1α, which can promote the proliferation and mobility of hepatocellular carcinoma cells. FUT11 may be a novel and effective target for blocking the hypoxia response of hepatocellular carcinoma cells.
缺氧促进肝细胞癌的进展。然而，已知肝细胞癌中的缺氧调节网络是有限的。因此，本研究旨在鉴定关键的与缺氧相关的基因，并探讨它们在肝细胞癌细胞中的作用和分子机制。通过生物信息学分析，首次鉴定 FUT11 为关键的与缺氧相关的基因。高 FUT11 mRNA 水平与不良的临床参数呈正相关。在常氧和缺氧条件下敲低 FUT11 均降低了肝细胞癌细胞的增殖、集落形成、迁移和侵袭。HIF1α 结合到 FUT11 的启动子上，并增加其转录和与肝细胞癌组织中 FUT11 的共表达。在 HIF1α 敲低细胞中转染 FUT11 过表达逆转了 HIF1α 抑制在缺氧条件下对肝细胞癌细胞增殖和迁移的抑制作用。因此，我们的研究结果表明，FUT11 是 HIF1α 的关键靶基因，可促进肝细胞癌细胞的增殖和迁移。FUT11 可能是阻断肝细胞癌细胞缺氧反应的新的有效靶点。
