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SENP1/HIF‐1α feedback loop modulates hypoxia‐induced cell proliferation, invasion, and EMT in human osteosarcoma cells
Author(s) -
Wang Xiaowei,
Liang Xiaoju,
Liang Huan,
Wang Bing
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26342
Subject(s) - downregulation and upregulation , gene knockdown , epithelial–mesenchymal transition , hypoxia (environmental) , cell growth , microbiology and biotechnology , cancer research , cell , cell migration , biology , apoptosis , tumor microenvironment , chemistry , biochemistry , gene , tumor cells , organic chemistry , oxygen
Hypoxia is an element intrinsic to most solid‐tumor microenvironments, including that of osteosarcoma (OS), and is associated with resistance to therapy, poor survival, and a malignant phenotype. The purpose of the present study was to investigate the role and underlying mechanism of SUMO‐specific protease 1 (SENP1)/hypoxia‐inducible factor‐1α (HIF‐1α) feedback loop in hypoxic microenvironment of OS. We observed that the expression of SENP1 was remarkably upregulated in OS cells. Additionally, there was a concomitant high expression of HIF‐1α and SENP1 in MG‐63 cells under a hypoxic microenvironment. Interestingly, blockage of HIF‐1α repressed the enhancement of SENP1. Moreover, knockdown of SENP1 with siRNA notably inhibited cell viability and accelerated cell apoptosis accompanied by a decrease in the expression of Bcl‐2 and an increase in the expression of Bax in MG‐63 cells following exposure to hypoxia. Furthermore, repression of SENP1 dramatically suppressed cell invasive ability through modulating epithelial‐mesenchymal transition (EMT) marked genes as reflected by the upregulation of E‐cadherin, as well as the downregulation of vimentin and N‐cadherin under hypoxic conditions. Most importantly, SENP1 positively regulated HIF‐1α expression level in the setting of hypoxic; subsequently, depletion of SENP1 expression markedly ameliorated vascular endothelial growth factor (VEGF) production triggered by hypoxia. Taken together, positive feedback loop between HIF‐1α and SENP1 in the regulating of the process of cell proliferation, invasion, and EMT in OS cells under hypoxic conditions, suggesting that the SENP1/HIF‐1α axis may serve as a new potential therapeutic agent for OS treatments.