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Ubiquitin-specific peptidase 39 regulates the process of proliferation and migration of human ovarian cancer via p53/p21 pathway and EMT

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Abstract

Ovarian cancer is one of the most lethal gynecological cancers; owning to its late detection and chemoresistance, understanding the pathogenesis of this malignant tumor is much critical. Previous studies have reported that ubiquitin-specific peptidase 39 (USP39) is generally overexpressed in a variety of cancers, including hepatocellular carcinoma, gastric cancer and so forth. Furthermore, USP39 is proved to be associated with the proliferation of malignant tumors. However, the function and mechanism of USP39 in ovarian cancer have not been elucidated. In the present study, we observed that USP39 was frequently overexpressed in human ovarian cancer and was highly correlated with TNM stage. Suppression of USP39 markedly inhibited the growth and migration of ovarian cancer cell lines HO-8910 and SKOV3 and induced cell cycle G2/M arrest. Moreover, knockdown of USP39 inhibited ovarian tumor growth in a xenograft model. In addition, our findings indicated that cell cycle arrest induced by USP39 knockdown might be involved in p53/p21 signaling pathway. Furthermore, we found that the depletion of USP39 inhibited the migration of ovarian cancer cells via blocking epithelial–mesenchymal transition. Taken together, these results suggest that USP39 may play vital roles in the genesis and progression and may serve as a potential biomarker for diagnosis and therapeutic target of ovarian cancer.

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Acknowledgements

This work was supported by the grants from the National Natural Science Foundation of China (81872045, 81470793), and the special fund for public welfare research institutes of Fujian Province (2017R1036-1, 2018R1036-4).

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Author notes

  1. Congcong Yan, Jiahui Yuan and Jiajia Xu have contributed equally to this work.

Authors and Affiliations

  1. Cancer Research Center, School of Medicine, Xiamen University, Xiamen, 361102, China

    Congcong Yan, Jiahui Yuan, Jiajia Xu, Gongye Zhang, Xiaomei Li, Tianhui Hu, Yubin Mao & Gang Song

  2. Department of Basic Medicine, School of Medicine, Xiamen University, Xiamen, 361102, China

    Bing Zhang, Xiaohua Huang & Yubin Mao

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  1. Congcong Yan
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  2. Jiahui Yuan
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  5. Xiaomei Li
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Correspondence to Yubin Mao or Gang Song.

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The authors declare no conflict of interests.

Ethical approval

The animal studies were approved by the Institutional Animal Care and Use Committee (IACUC No. XMULAC20180056) of Xiamen University, Fujian. Animal experiments were approved by the Laboratory Animal Ethics Committee of Xiamen University.

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Yan, C., Yuan, J., Xu, J. et al. Ubiquitin-specific peptidase 39 regulates the process of proliferation and migration of human ovarian cancer via p53/p21 pathway and EMT. Med Oncol 36, 95 (2019). https://doi.org/10.1007/s12032-019-1308-7

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  • DOI: https://doi.org/10.1007/s12032-019-1308-7

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