Research Papers:

MicroRNA-30c-5p ameliorates hypoxia-reoxygenation-induced tubular epithelial cell injury via HIF1α stabilization by targeting SOCS3

Yan-Fang Zou, Wei-Tang Liao, Zong-Jie Fu, Qian Zhao, Yong-Xi Chen and Wen Zhang _

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Oncotarget. 2017; 8:92801-92814. https://doi.org/10.18632/oncotarget.21582

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Yan-Fang Zou1, Wei-Tang Liao1, Zong-Jie Fu1, Qian Zhao2, Yong-Xi Chen1 and Wen Zhang1

1Department of Nephrology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, PR China

2Cellular Differentiation and Apoptosis Laboratory, Key Laboratory of National Ministry of Education, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, PR China

Correspondence to:

Wen Zhang, email: [email protected]

Keywords: hypoxia-reoxygenation, microRNA, apoptosis, hypoxia-inducible factor-1α

Received: July 10, 2017     Accepted: September 03, 2017     Published: October 06, 2017


The cellular hypoxia-reoxygenation (H/R) model is an ideal method to study ischemia-reperfusion injury, which is associated with high mortality. The role of microRNA-30c-5p (miR-30c-5p) in the H/R epithelial cell model remains unknown. In the current study, we observed a significant reduction in apoptosis when miR-30c-5p was up-regulated. We also found decreased levels of C-caspase-3 (C-CASP3) and Bcl-2-associated X (BAX) proteins and increased levels of B-cell lymphoma-2 (BCL2). Epidermal growth factor receptor (EGFR) showed similar results. Down-regulating miR-30c-5p increased the levels of apoptosis and C-CASP3 and BAX expression; additionally, cell proliferation was inhibited. Hypoxia-inducible factor 1α (HIF1α) protein expression levels were up-regulated in response to up-regulation of miR-30c-5p expression. The anti-apoptotic and proliferative effects of miR-30c-5p decreased significantly after the HIF1α protein levels were knocked down. Using a luciferase reporter assay, we confirmed that miR-30c-5p targets suppressor of cytokine signaling-3 (SOCS3). HIF1α levels increased when SOCS3 was blocked. Our data show that SOCS3 expression enhances apoptosis in the H/R model. In conclusion, up-regulating miR-30c-5p protects cells from H/R -induced apoptosis and induces cell proliferation; furthermore, HIF1α markedly contributes to this protective effect. MiR-30c-5p stabilizes HIF1α expression by targeting SOCS3 to achieve anti-apoptotic and proliferative effects.

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