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...
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| Format: | Article |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.607021/full |
| _version_ | 1818866151582597120 |
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| author | Yiwei Liu Yiwei Liu Yiwei Liu Hairong Chen Xiangcheng Li Xiangcheng Li Xiangcheng Li Feng Zhang Feng Zhang Feng Zhang Lianbao Kong Lianbao Kong Lianbao Kong Xuehao Wang Xuehao Wang Xuehao Wang Jin Bai Jin Bai Xiaofeng Wu Xiaofeng Wu Xiaofeng Wu |
| author_facet | Yiwei Liu Yiwei Liu Yiwei Liu Hairong Chen Xiangcheng Li Xiangcheng Li Xiangcheng Li Feng Zhang Feng Zhang Feng Zhang Lianbao Kong Lianbao Kong Lianbao Kong Xuehao Wang Xuehao Wang Xuehao Wang Jin Bai Jin Bai Xiaofeng Wu Xiaofeng Wu Xiaofeng Wu |
| author_sort | Yiwei Liu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T10:58:53Z |
| format | Article |
| id | doaj.art-8cdb37f00bc34fababd3f08a536a88a1 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-19T10:58:53Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-8cdb37f00bc34fababd3f08a536a88a12022-12-21T20:24:42ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-02-011110.3389/fonc.2021.607021607021PSMC2 Regulates Cell Cycle Progression Through the p21/Cyclin D1 Pathway and Predicts a Poor Prognosis in Human Hepatocellular CarcinomaYiwei Liu0Yiwei Liu1Yiwei Liu2Hairong Chen3Xiangcheng Li4Xiangcheng Li5Xiangcheng Li6Feng Zhang7Feng Zhang8Feng Zhang9Lianbao Kong10Lianbao Kong11Lianbao Kong12Xuehao Wang13Xuehao Wang14Xuehao Wang15Jin Bai16Jin Bai17Xiaofeng Wu18Xiaofeng Wu19Xiaofeng Wu20Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaKey Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, ChinaNHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, ChinaDepartment of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaKey Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, ChinaNHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaKey Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, ChinaNHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaKey Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, ChinaNHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaKey Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, ChinaNHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, ChinaCancer Institute, Xuzhou Medical University, Xuzhou, ChinaCenter of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaKey Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, ChinaNHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, ChinaProteasome 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.https://www.frontiersin.org/articles/10.3389/fonc.2021.607021/fullPSMC2hepatocellular carcinomap21cell proliferationcarcinogenesis |
| spellingShingle | Yiwei Liu Yiwei Liu Yiwei Liu Hairong Chen Xiangcheng Li Xiangcheng Li Xiangcheng Li Feng Zhang Feng Zhang Feng Zhang Lianbao Kong Lianbao Kong Lianbao Kong Xuehao Wang Xuehao Wang Xuehao Wang Jin Bai Jin Bai Xiaofeng Wu Xiaofeng Wu Xiaofeng Wu PSMC2 Regulates Cell Cycle Progression Through the p21/Cyclin D1 Pathway and Predicts a Poor Prognosis in Human Hepatocellular Carcinoma Frontiers in Oncology PSMC2 hepatocellular carcinoma p21 cell proliferation carcinogenesis |
| 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 | PSMC2 hepatocellular carcinoma p21 cell proliferation carcinogenesis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.607021/full |
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