SENP1/HIF‐1α feedback loop modulates hypoxia‐induced cell proliferation, invasion, and EMT in human osteosarcoma cells. Issue 2 (27th September 2017)

• Record Type: Journal Article
• Authors: Wang, Xiaowei; Liang, Xiaoju; Liang, Huan; Wang, Bing
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 2(2018)
• Page Start: 1819
• Page End: 1826
• Publication Date: 2017-09-27
• Subjects: hypoxia -- migration -- osteosarcoma (OS) -- SENP1/HIF‐1α axis; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.26342
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract : 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. Abstract : 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.