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PSMD8 can serve as potential biomarker and therapeutic target of the PSMD family in ovarian cancer: based on bioinformatics analysis and in vitro validation

BACKGROUND: The ubiquity-proteasome system is an indispensable mechanism for regulating intracellular protein degradation, thereby affecting human antigen processing, signal transduction, and cell cycle regulation. We used bioinformatics database to predict the expression and related roles of all me...

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Autores principales: Li, Xiao, Li, Xinru, Hu, Yuexin, Liu, Ouxuan, Wang, Yuxuan, Li, Siting, Yang, Qing, Lin, Bei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10286491/
https://www.ncbi.nlm.nih.gov/pubmed/37349676
http://dx.doi.org/10.1186/s12885-023-11017-8
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author Li, Xiao
Li, Xinru
Hu, Yuexin
Liu, Ouxuan
Wang, Yuxuan
Li, Siting
Yang, Qing
Lin, Bei
author_facet Li, Xiao
Li, Xinru
Hu, Yuexin
Liu, Ouxuan
Wang, Yuxuan
Li, Siting
Yang, Qing
Lin, Bei
author_sort Li, Xiao
collection PubMed
description BACKGROUND: The ubiquity-proteasome system is an indispensable mechanism for regulating intracellular protein degradation, thereby affecting human antigen processing, signal transduction, and cell cycle regulation. We used bioinformatics database to predict the expression and related roles of all members of the PSMD family in ovarian cancer. Our findings may provide a theoretical basis for early diagnosis, prognostic assessment, and targeted therapy of ovarian cancer. METHODS: GEPIA, cBioPortal, and Kaplan–Meier Plotter databases were used to analyze the mRNA expression levels, gene variation, and prognostic value of PSMD family members in ovarian cancer. PSMD8 was identified as the member with the best prognostic value. The TISIDB database was used to analyze the correlation between PSMD8 and immunity, and the role of PSMD8 in ovarian cancer tissue was verified by immunohistochemical experiments. The relationship of PSMD8 expression with clinicopathological parameters and survival outcomes of ovarian cancer patients was analyzed. The effects of PSMD8 on malignant biological behaviors of invasion, migration, and proliferation of ovarian cancer cells were studied by in vitro experiments. RESULTS: The expression levels of PSMD8/14 mRNA in ovarian cancer tissues were significantly higher than those in normal ovarian tissues, and the expression levels of PSMD2/3/4/5/8/11/12/14 mRNA were associated with prognosis. Up-regulation of PSMD4/8/14 mRNA expression was associated with poor OS, and the up-regulation of PSMD2/3/5/8 mRNA expression was associated with poor PFS in patients with ovarian serous carcinomas. Gene function and enrichment analysis showed that PSMD8 is mainly involved in biological processes such as energy metabolism, DNA replication, and protein synthesis. Immunohistochemical experiments showed that PSMD8 was mainly expressed in the cytoplasm and the expression level was correlated with FIGO stage. Patients with high PSMD8 expression had poor prognosis. Overexpression of PSMD8 significantly enhanced the proliferation, migration, and invasion abilities in ovarian cancer cells. CONCLUSION: We observed different degrees of abnormal expression of members of PSMD family in ovarian cancer. Among these, PSMD8 was significantly overexpressed in ovarian malignant tissue, and was associated with poor prognosis. PSMDs, especially PSMD8, can serve as potential diagnostic and prognostic biomarkers and therapeutic targets in ovarian cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11017-8.
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spelling pubmed-102864912023-06-23 PSMD8 can serve as potential biomarker and therapeutic target of the PSMD family in ovarian cancer: based on bioinformatics analysis and in vitro validation Li, Xiao Li, Xinru Hu, Yuexin Liu, Ouxuan Wang, Yuxuan Li, Siting Yang, Qing Lin, Bei BMC Cancer Research BACKGROUND: The ubiquity-proteasome system is an indispensable mechanism for regulating intracellular protein degradation, thereby affecting human antigen processing, signal transduction, and cell cycle regulation. We used bioinformatics database to predict the expression and related roles of all members of the PSMD family in ovarian cancer. Our findings may provide a theoretical basis for early diagnosis, prognostic assessment, and targeted therapy of ovarian cancer. METHODS: GEPIA, cBioPortal, and Kaplan–Meier Plotter databases were used to analyze the mRNA expression levels, gene variation, and prognostic value of PSMD family members in ovarian cancer. PSMD8 was identified as the member with the best prognostic value. The TISIDB database was used to analyze the correlation between PSMD8 and immunity, and the role of PSMD8 in ovarian cancer tissue was verified by immunohistochemical experiments. The relationship of PSMD8 expression with clinicopathological parameters and survival outcomes of ovarian cancer patients was analyzed. The effects of PSMD8 on malignant biological behaviors of invasion, migration, and proliferation of ovarian cancer cells were studied by in vitro experiments. RESULTS: The expression levels of PSMD8/14 mRNA in ovarian cancer tissues were significantly higher than those in normal ovarian tissues, and the expression levels of PSMD2/3/4/5/8/11/12/14 mRNA were associated with prognosis. Up-regulation of PSMD4/8/14 mRNA expression was associated with poor OS, and the up-regulation of PSMD2/3/5/8 mRNA expression was associated with poor PFS in patients with ovarian serous carcinomas. Gene function and enrichment analysis showed that PSMD8 is mainly involved in biological processes such as energy metabolism, DNA replication, and protein synthesis. Immunohistochemical experiments showed that PSMD8 was mainly expressed in the cytoplasm and the expression level was correlated with FIGO stage. Patients with high PSMD8 expression had poor prognosis. Overexpression of PSMD8 significantly enhanced the proliferation, migration, and invasion abilities in ovarian cancer cells. CONCLUSION: We observed different degrees of abnormal expression of members of PSMD family in ovarian cancer. Among these, PSMD8 was significantly overexpressed in ovarian malignant tissue, and was associated with poor prognosis. PSMDs, especially PSMD8, can serve as potential diagnostic and prognostic biomarkers and therapeutic targets in ovarian cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11017-8. BioMed Central 2023-06-22 /pmc/articles/PMC10286491/ /pubmed/37349676 http://dx.doi.org/10.1186/s12885-023-11017-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Li, Xiao
Li, Xinru
Hu, Yuexin
Liu, Ouxuan
Wang, Yuxuan
Li, Siting
Yang, Qing
Lin, Bei
PSMD8 can serve as potential biomarker and therapeutic target of the PSMD family in ovarian cancer: based on bioinformatics analysis and in vitro validation
title PSMD8 can serve as potential biomarker and therapeutic target of the PSMD family in ovarian cancer: based on bioinformatics analysis and in vitro validation
title_full PSMD8 can serve as potential biomarker and therapeutic target of the PSMD family in ovarian cancer: based on bioinformatics analysis and in vitro validation
title_fullStr PSMD8 can serve as potential biomarker and therapeutic target of the PSMD family in ovarian cancer: based on bioinformatics analysis and in vitro validation
title_full_unstemmed PSMD8 can serve as potential biomarker and therapeutic target of the PSMD family in ovarian cancer: based on bioinformatics analysis and in vitro validation
title_short PSMD8 can serve as potential biomarker and therapeutic target of the PSMD family in ovarian cancer: based on bioinformatics analysis and in vitro validation
title_sort psmd8 can serve as potential biomarker and therapeutic target of the psmd family in ovarian cancer: based on bioinformatics analysis and in vitro validation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10286491/
https://www.ncbi.nlm.nih.gov/pubmed/37349676
http://dx.doi.org/10.1186/s12885-023-11017-8
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