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Tytuł:
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Deubiquitylase PSMD14 inhibits autophagy to promote ovarian cancer progression via stabilization of LRPPRC.
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Autorzy:
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Zhao Z; State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Xu H; Departments of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital l & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.
Wei Y; Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, China.
Sun L; Departments of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital l & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China; Departments of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: .
Song Y; State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: .
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Źródło:
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Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2023 Feb; Vol. 1869 (2), pp. 166594. Date of Electronic Publication: 2022 Nov 01.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: Amsterdam : Elsevier
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MeSH Terms:
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Autophagy*/genetics
Neoplasm Proteins*/metabolism
Ovarian Neoplasms*/pathology
Proteasome Endopeptidase Complex*/genetics
Proteasome Endopeptidase Complex*/metabolism
Trans-Activators*/genetics
Trans-Activators*/metabolism
Female ; Humans ; Cell Line, Tumor ; Proteolysis ; Ubiquitination ; Protein Stability
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Contributed Indexing:
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Keywords: Autophagy; Deubiquitylase; Metastasis; Ovarian cancer; Proliferation
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Substance Nomenclature:
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0 (LRPPRC protein, human)
0 (Neoplasm Proteins)
EC 3.4.25.1 (Proteasome Endopeptidase Complex)
0 (PSMD14 protein, human)
0 (Trans-Activators)
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Entry Date(s):
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Date Created: 20221103 Date Completed: 20230103 Latest Revision: 20230217
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Update Code:
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20240105
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DOI:
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10.1016/j.bbadis.2022.166594
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PMID:
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36328147
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Autophagy is a key cellular process, which exists in many tumors and plays dual roles in tumor promotion and suppression. However, the role and mechanism of aberrant autophagy in ovarian cancer remains unclear. Ubiquitin-proteasome pathway is the most important pathway for specific protein degradation. Deubiquitinases (DUBs) have crucial roles in all the stages of tumorigenesis and progression. Herein, we explore the DUBs which contribute to aberrant autophagy in ovarian cancer. TCGA data analysis shows that the autophagy level is suppressed, and the selective autophagy receptor SQSTM1/p62 is abnormally high expressed in ovarian cancer. We screen and identify that the deubiquitinase PSMD14 negatively regulates autophagy level. Functional studies show that increased PSMD14 expression remarkably enhances ovarian cancer cells malignancy, whereas knockdown of PSMD14 has the opposite effect. Furthermore, in vivo assays show that knockdown of PSMD14 inhibits the growth, lung and abdominal metastasis of ovarian cancer. Mechanistically, PSMD14 directly interacts with LRPPRC and inhibits its ubiquitination, thereby inhibiting autophagy through LRPPRC/Beclin1-Bcl-2/SQSTM1 signaling pathway. Next, we demonstrate that PSMD14 is upregulated in ovarian cancer and high expression of PSMD14 positively correlates with LRPPRC. Taken together, we clarify the role of autophagy in regulating the ovarian cancer phenotype and provide insights into regulatory mechanism of autophagy in ovarian cancer.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022. Published by Elsevier B.V.)
