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PSMC2 Regulates Cell Cycle Progression Through the p21/Cyclin D1 Pathway and Predicts a Poor Prognosis in Human Hepatocellular Carcinoma
Proteasome 26S subunit ATPase 2 (PSMC2) plays a pathogenic role in various cancers. However, its function and molecular mechanism in hepatocellular carcinoma (HCC) remain unknown. In this study, tissue microarray (TMA) analysis showed that PSMC2 is highly expressed in HCC tumors and correlates with...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952995/ https://www.ncbi.nlm.nih.gov/pubmed/33718159 http://dx.doi.org/10.3389/fonc.2021.607021 |
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author | Liu, Yiwei Chen, Hairong Li, Xiangcheng Zhang, Feng Kong, Lianbao Wang, Xuehao Bai, Jin Wu, Xiaofeng |
author_facet | Liu, Yiwei Chen, Hairong Li, Xiangcheng Zhang, Feng Kong, Lianbao Wang, Xuehao Bai, Jin Wu, Xiaofeng |
author_sort | Liu, Yiwei |
collection | PubMed |
description | Proteasome 26S subunit ATPase 2 (PSMC2) plays a pathogenic role in various cancers. However, its function and molecular mechanism in hepatocellular carcinoma (HCC) remain unknown. In this study, tissue microarray (TMA) analysis showed that PSMC2 is highly expressed in HCC tumors and correlates with poor overall and disease-free survival in HCC patients. Multivariate Cox regression analysis revealed that PSMC2 is an independent prognostic factor for HCC patients. Furthermore, our results showed that PSMC2 knockdown inhibited cell proliferation and suppressed tumorigenesis in vivo. Knockdown of PSMC2 increased the expression of p21 and therefore decreased the expression of cyclin D1. Dual-luciferase reporter assays indicated that depletion of PSMC2 significantly enhanced the promoter activity of p21. Importantly, PSMC2 knockdown-induced phenotypes were also rescued by downregulation of P21. Taken together, our data suggest that PSMC2 promotes HCC cell proliferation and cell cycle progression through the p21/cyclin D1 signaling pathway and could be a promising diagnostic and therapeutic target for HCC patients. |
format | Online Article Text |
id | pubmed-7952995 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79529952021-03-13 PSMC2 Regulates Cell Cycle Progression Through the p21/Cyclin D1 Pathway and Predicts a Poor Prognosis in Human Hepatocellular Carcinoma Liu, Yiwei Chen, Hairong Li, Xiangcheng Zhang, Feng Kong, Lianbao Wang, Xuehao Bai, Jin Wu, Xiaofeng Front Oncol Oncology Proteasome 26S subunit ATPase 2 (PSMC2) plays a pathogenic role in various cancers. However, its function and molecular mechanism in hepatocellular carcinoma (HCC) remain unknown. In this study, tissue microarray (TMA) analysis showed that PSMC2 is highly expressed in HCC tumors and correlates with poor overall and disease-free survival in HCC patients. Multivariate Cox regression analysis revealed that PSMC2 is an independent prognostic factor for HCC patients. Furthermore, our results showed that PSMC2 knockdown inhibited cell proliferation and suppressed tumorigenesis in vivo. Knockdown of PSMC2 increased the expression of p21 and therefore decreased the expression of cyclin D1. Dual-luciferase reporter assays indicated that depletion of PSMC2 significantly enhanced the promoter activity of p21. Importantly, PSMC2 knockdown-induced phenotypes were also rescued by downregulation of P21. Taken together, our data suggest that PSMC2 promotes HCC cell proliferation and cell cycle progression through the p21/cyclin D1 signaling pathway and could be a promising diagnostic and therapeutic target for HCC patients. Frontiers Media S.A. 2021-02-26 /pmc/articles/PMC7952995/ /pubmed/33718159 http://dx.doi.org/10.3389/fonc.2021.607021 Text en Copyright © 2021 Liu, Chen, Li, Zhang, Kong, Wang, Bai and Wu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Liu, Yiwei Chen, Hairong Li, Xiangcheng Zhang, Feng Kong, Lianbao Wang, Xuehao Bai, Jin Wu, Xiaofeng PSMC2 Regulates Cell Cycle Progression Through the p21/Cyclin D1 Pathway and Predicts a Poor Prognosis in Human Hepatocellular Carcinoma |
title | PSMC2 Regulates Cell Cycle Progression Through the p21/Cyclin D1 Pathway and Predicts a Poor Prognosis in Human Hepatocellular Carcinoma |
title_full | PSMC2 Regulates Cell Cycle Progression Through the p21/Cyclin D1 Pathway and Predicts a Poor Prognosis in Human Hepatocellular Carcinoma |
title_fullStr | PSMC2 Regulates Cell Cycle Progression Through the p21/Cyclin D1 Pathway and Predicts a Poor Prognosis in Human Hepatocellular Carcinoma |
title_full_unstemmed | PSMC2 Regulates Cell Cycle Progression Through the p21/Cyclin D1 Pathway and Predicts a Poor Prognosis in Human Hepatocellular Carcinoma |
title_short | PSMC2 Regulates Cell Cycle Progression Through the p21/Cyclin D1 Pathway and Predicts a Poor Prognosis in Human Hepatocellular Carcinoma |
title_sort | psmc2 regulates cell cycle progression through the p21/cyclin d1 pathway and predicts a poor prognosis in human hepatocellular carcinoma |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952995/ https://www.ncbi.nlm.nih.gov/pubmed/33718159 http://dx.doi.org/10.3389/fonc.2021.607021 |
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