Qiu Jun-Jun, Lin Xiao-Jing, Zheng Ting-Ting, Tang Xiao-Yan, Hua Ke-Qin
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China,
Obstetrics and Gynecology Department of Shanghai Medical College, Fudan University, Shanghai 200032, China,
Onco Targets Ther. 2018 Dec 14;11:9101-9110. doi: 10.2147/OTT.S173816. eCollection 2018.
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.
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.
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.
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.
缺氧是触发包括上皮性卵巢癌（EOC）在内的各种肿瘤细胞凋亡的关键应激因素。先前的研究在一些肿瘤中鉴定出一种缺氧上调的长链非编码RNA，名为“缺氧诱导因子1的天然反义转录本（aHIF）”。然而，aHIF对EOC的作用仍不清楚。在此，我们旨在研究aHIF在缺氧条件下EOC进展中的表达、功能及潜在机制。
检测EOC组织中aHIF的表达水平。进行体外和体内实验以探究aHIF在缺氧诱导的EOC进展中的功能和机制。
EOC组织中aHIF水平升高，且在EOC细胞中缺氧可使其上调。功能数据显示，敲低aHIF可加速缺氧条件下的细胞凋亡，并在体内抑制EOC的肿瘤发生和肿瘤生长。此外，aHIF过表达可抑制EOC细胞在缺氧条件下的凋亡并增强细胞增殖。机制上，某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aHIF在缺氧条件下对EOC凋亡和生长的调节作用。
这些数据提供了首个令人信服的证据，即aHIF可能通过在缺氧条件下激活线粒体凋亡途径来抑制EOC凋亡，从而促进肿瘤生长。我们的研究结果有助于阐明长链非编码RNA在缺氧诱导的EOC进展中的作用。
