Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2

Dysregulation of deubiquitination has been reported to contribute to carcinogenesis. However, the function and mechanism of deubiquitinating enzyme 26S proteasome non‐ATPase regulatory subunit 14 (PSMD14) in the progression of ovarian cancer (OV), the deadliest gynecological cancer, still remains to...

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Autores principales:	Tianshui Sun, Zhuonan Liu, Fangfang Bi, Qing Yang
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	cancer metabolism deubiquitination OPA PKM2 PSMD14 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5d4589114cba4195aeec647c7216aa6a
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spelling	oai:doaj.org-article:5d4589114cba4195aeec647c7216aa6a2021-12-02T10:31:06ZDeubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM21878-02611574-789110.1002/1878-0261.13076https://doaj.org/article/5d4589114cba4195aeec647c7216aa6a2021-12-01T00:00:00Zhttps://doi.org/10.1002/1878-0261.13076https://doaj.org/toc/1574-7891https://doaj.org/toc/1878-0261Dysregulation of deubiquitination has been reported to contribute to carcinogenesis. However, the function and mechanism of deubiquitinating enzyme 26S proteasome non‐ATPase regulatory subunit 14 (PSMD14) in the progression of ovarian cancer (OV), the deadliest gynecological cancer, still remains to be characterized. The present study demonstrated that PSMD14 was overexpressed in OV tissues and its higher levels correlated with a higher International Federation of Gynecology and Obstetrics (FIGO) stage in OV patients. A high level of PSMD14 expression was related to poor survival in OV patients. Knockdown and overexpression experiments elucidated that PSMD14 stimulated OV cell proliferation, invasion, and migration in vitro. Repression of PSMD14 suppressed OV tumor growth in vivo. PSMD14 inhibitor O‐phenanthroline (OPA) effectively attenuated malignant behaviors of OV cells in vitro and OV tumor growth in vivo. Mechanistically, we uncovered that PSMD14 was involved in post‐translational regulation of pyruvate kinase M2 isoform (PKM2). PSMD14 decreased K63‐linked ubiquitination on PKM2, downregulated the ratio of PKM2 tetramers to dimers and monomers, and subsequently diminished pyruvate kinase activity and induced nuclear translocation of PKM2, contributing to aerobic glycolysis in OV cells. Collectively, our findings highlight the potential roles of PSMD14 as a biomarker and therapeutic candidate for OV.Tianshui SunZhuonan LiuFangfang BiQing YangWileyarticlecancer metabolismdeubiquitinationOPAPKM2PSMD14Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Oncology, Vol 15, Iss 12, Pp 3639-3658 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancer metabolism deubiquitination OPA PKM2 PSMD14 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	cancer metabolism deubiquitination OPA PKM2 PSMD14 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Tianshui Sun Zhuonan Liu Fangfang Bi Qing Yang Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2
description	Dysregulation of deubiquitination has been reported to contribute to carcinogenesis. However, the function and mechanism of deubiquitinating enzyme 26S proteasome non‐ATPase regulatory subunit 14 (PSMD14) in the progression of ovarian cancer (OV), the deadliest gynecological cancer, still remains to be characterized. The present study demonstrated that PSMD14 was overexpressed in OV tissues and its higher levels correlated with a higher International Federation of Gynecology and Obstetrics (FIGO) stage in OV patients. A high level of PSMD14 expression was related to poor survival in OV patients. Knockdown and overexpression experiments elucidated that PSMD14 stimulated OV cell proliferation, invasion, and migration in vitro. Repression of PSMD14 suppressed OV tumor growth in vivo. PSMD14 inhibitor O‐phenanthroline (OPA) effectively attenuated malignant behaviors of OV cells in vitro and OV tumor growth in vivo. Mechanistically, we uncovered that PSMD14 was involved in post‐translational regulation of pyruvate kinase M2 isoform (PKM2). PSMD14 decreased K63‐linked ubiquitination on PKM2, downregulated the ratio of PKM2 tetramers to dimers and monomers, and subsequently diminished pyruvate kinase activity and induced nuclear translocation of PKM2, contributing to aerobic glycolysis in OV cells. Collectively, our findings highlight the potential roles of PSMD14 as a biomarker and therapeutic candidate for OV.
format	article
author	Tianshui Sun Zhuonan Liu Fangfang Bi Qing Yang
author_facet	Tianshui Sun Zhuonan Liu Fangfang Bi Qing Yang
author_sort	Tianshui Sun
title	Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2
title_short	Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2
title_full	Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2
title_fullStr	Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2
title_full_unstemmed	Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2
title_sort	deubiquitinase psmd14 promotes ovarian cancer progression by decreasing enzymatic activity of pkm2
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/5d4589114cba4195aeec647c7216aa6a
work_keys_str_mv	AT tianshuisun deubiquitinasepsmd14promotesovariancancerprogressionbydecreasingenzymaticactivityofpkm2 AT zhuonanliu deubiquitinasepsmd14promotesovariancancerprogressionbydecreasingenzymaticactivityofpkm2 AT fangfangbi deubiquitinasepsmd14promotesovariancancerprogressionbydecreasingenzymaticactivityofpkm2 AT qingyang deubiquitinasepsmd14promotesovariancancerprogressionbydecreasingenzymaticactivityofpkm2
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Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2

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