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Natural antisense transcript of hypoxia-inducible factor 1 regulates hypoxic cell apoptosis in epithelial ovarian cancer

Authors Qiu J, Lin X, Zheng T, Tang X, Hua K

Received 11 May 2018

Accepted for publication 27 August 2018

Published 14 December 2018 Volume 2018:11 Pages 9101—9110

DOI https://doi.org/10.2147/OTT.S173816

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Federico Perche


Jun-jun Qiu,1–3 Xiao-jing Lin,1–3 Ting-ting Zheng,1–3 Xiao-yan Tang,1–3 Ke-qin Hua1–3

1Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China; 2Obstetrics and Gynecology Department of Shanghai Medical College, Fudan University, Shanghai 200032, China; 3Department of Gynecology, Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai 200011, China

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.

Keywords: lncRNA, hypoxia, microenvironment, tumor growth
 

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