SENP1 desensitizes hypoxic ovarian cancer cells to cisplatin by up-regulating HIF-1α.

Qilin Ao,Wenjing Su,Lei Cai,Shuang Guo,Lei Huang

doi:10.1038/srep16396

Abstract

Hypoxia-inducible factor 1 alpha (HIF-1α) is closely related to chemoresistance of ovarian cancers. Although it is reported that HIF-1α can be regulated by Sentrin/SUMO-specific protease 1 (SENP1), the effects of SENP1 on HIF-1α is still controversial. In this study, we identified that SENP1 positively regulated the expression of HIF-1α by deSUMOylation and weakened the sensitivity of hypoxic ovarian cancer cells to cisplatin. These results indicate that SENP1 is a positive regulator of HIF-1α and plays a negative role in ovarian cancer chemotherapy.

Highlights

Hypoxia-inducible factor 1 alpha (HIF-1α) is closely related to chemoresistance of ovarian cancers
Cell Counting Kit-8 (CCK8) and FCM showed that 150 μ M or 200 μ M CoCl2 had no significant impact on the basic proliferation and cell apoptosis rate of SKOV3 (P < 0 .05) (Fig. 1B,C)
MG132 increased HIF-1α SUMOylation, suggesting that the level of SUMOylated HIF-1α was controlled by a proteasome-dependent mechanism. These results suggested that SENP1 maintained HIF-1α stability through desumoylation, which was followed by the interdiction of a proteasome-mediated HIF-1α degradation

Summary

Introduction

Hypoxia-inducible factor 1 alpha (HIF-1α) is closely related to chemoresistance of ovarian cancers. We identified that SENP1 positively regulated the expression of HIF-1α by deSUMOylation and weakened the sensitivity of hypoxic ovarian cancer cells to cisplatin. These results indicate that SENP1 is a positive regulator of HIF-1α and plays a negative role in ovarian cancer chemotherapy. HIF-1α plays important roles in ovarian cancer chemoresistance[5,6], which confers extra significance to correlated studies. These years, modifications other than hydroxylation such as SUMOylation and deSUMOylation have been discovered to participate in HIF-1α regulation. CoCl2 has been widely used to simulate hypoxia condition in numerous systems including ovarian cancer

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Results

Conclusion