Natural antisense transcript of hypoxia-inducible factor 1 regulates hypoxic cell apoptosis in epithelial ovarian cancer
Natural antisense transcript of hypoxia-inducible factor 1 regulates hypoxic cell apoptosis in epithelial ovarian cancer
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DOI：
10.2147/ott.s173816
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发表时间：
2018-12
影响因子：
4
通讯作者：
J. Qiu;Xiao-jing Lin;Ting-ting Zheng;Xiaoyan Tang;K. Hua
中科院分区：
文献类型：
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作者：
J. Qiu;Xiao-jing Lin;Ting-ting Zheng;Xiaoyan Tang;K. Hua
在包括上皮性卵巢癌（EOC）在内的多种肿瘤中，缺氧是触发细胞凋亡的关键应激因素。先前的研究在一些肿瘤中发现了一种低氧上调的lncRNA，名为“天然反义转录物缺氧诱导因子1 （aHIF）”。然而，aHIF对EOC的贡献仍不清楚。在此，我们旨在探讨缺氧条件下aHIF在EOC进展中的表达、功能和潜在机制。材料与方法检测aHIF在EOC组织中的表达水平。通过体外和体内实验，探讨aHIF在缺氧诱导的EOC进展中的作用和机制。结果EOC组织中aHIF水平升高，缺氧使aHIF水平上调。功能数据显示，aHIF敲低可加速缺氧条件下细胞凋亡，抑制EOC肿瘤发生和肿瘤生长。缺氧条件下，过表达aHIF可抑制细胞凋亡，增强细胞增殖。机制上，一些关键的线粒体凋亡途径相关基因，包括Bcl-2、Bax、Caspase-7和Caspase-9的失调可能部分解释了缺氧条件下ahif调控的EOC凋亡和生长。结论缺氧条件下，aHIF可能通过激活线粒体凋亡通路抑制EOC凋亡，从而促进肿瘤生长。我们的研究结果有助于阐明lncRNA在缺氧诱导的EOC进展中的作用。
Purpose Hypoxia is a key stress that triggers apoptosis in various tumors, including epithelial ovarian cancer (EOC). Previous researches identified a hypoxia-upregulated lncRNA named “a natural antisense transcript of hypoxia-inducible factor 1 (aHIF)” in some tumors. However, the contribution of aHIF to EOC remains unclear. Here, we aimed to investigate the expression, function, and underlying mechanisms of aHIF in EOC progression under hypoxia. Materials and methods Expression levels of aHIF in EOC tissues were tested. In vitro and in vivo assays were conducted to explore the function and mechanism of aHIF in hypoxia-induced EOC progression. Results aHIF levels were increased in EOC tissues and were upregulated by hypoxia in EOC cells. Functional data revealed that aHIF knockdown accelerated cell apoptosis under hypoxia and inhibited EOC tumorigenesis and tumor growth in vivo. Additionally, aHIF overexpression inhibited cell apoptosis and enhanced cell proliferation under hypoxia in EOC. Mechanistically, the dysregulation of certain key mitochondrial apoptosis pathway-related genes, including Bcl-2, Bax, Caspase-7, and Caspase-9, may partially explain aHIF-regulated EOC apoptosis and growth under hypoxia. Conclusion These data provide the first convincing evidence that aHIF may inhibit EOC apoptosis and thereby promote tumor growth through activation of the mitochondrial apoptosis pathway under hypoxia. Our findings help clarify the role of lncRNA in hypoxia-induced EOC progression.