FBXO10 Drives Hepatocellular Carcinoma Proliferation via K63-Linked Ubiquitination and Stabilization of FRMPD1
Aberrant ubiquitination drives hepatocellular carcinoma (HCC) progression, yet the role of FBXO10—a key F-box E3 ubiquitin ligase component—remains uncharacterized. Through bioinformatics analyses and functional validation, we establish FBXO10 as a critical oncogenic driver in HCC. Transcriptomic da...
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2025-05-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/47/6/391 |
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| author | Wuguang Liu Bin Xu Kashif Kifayat Yuhong Xie Xiaolong Liu Chengyong Dong Liming Wang |
| author_facet | Wuguang Liu Bin Xu Kashif Kifayat Yuhong Xie Xiaolong Liu Chengyong Dong Liming Wang |
| author_sort | Wuguang Liu |
| collection | DOAJ |
| description | Aberrant ubiquitination drives hepatocellular carcinoma (HCC) progression, yet the role of FBXO10—a key F-box E3 ubiquitin ligase component—remains uncharacterized. Through bioinformatics analyses and functional validation, we establish FBXO10 as a critical oncogenic driver in HCC. Transcriptomic data from public databases (TIMER, UALCAN, GEO) revealed significant FBXO10 upregulation in HCC tissues, with elevated expression predicting advanced tumor stage, metastasis, and reduced survival. Functionally, FBXO10 silencing suppressed HCC cell proliferation while its overexpression promoted tumor growth. Mechanistic studies revealed that FBXO10 directly interacts with FRMPD1 to mediate its K63-linked polyubiquitination and stabilization, independent of transcriptional regulation. FRMPD1 restoration rescued FBXO10-mediated proliferation, confirming its role as the key downstream effector. Clinically, FBXO10 expression correlated with TP53 mutations and adverse clinicopathological features. Our findings reveal a novel FBXO10–FRMPD1 axis promoting hepatocarcinogenesis through post-translational stabilization, positioning FBXO10 as both a prognostic biomarker and therapeutic target in HCC. |
| format | Article |
| id | doaj-art-aa8fa4d4a1f84511a6be5310f3169075 |
| institution | Kabale University |
| issn | 1467-3037 1467-3045 |
| language | English |
| publishDate | 2025-05-01 |
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| series | Current Issues in Molecular Biology |
| spelling | doaj-art-aa8fa4d4a1f84511a6be5310f31690752025-08-20T03:26:11ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-05-0147639110.3390/cimb47060391FBXO10 Drives Hepatocellular Carcinoma Proliferation via K63-Linked Ubiquitination and Stabilization of FRMPD1Wuguang Liu0Bin Xu1Kashif Kifayat2Yuhong Xie3Xiaolong Liu4Chengyong Dong5Liming Wang6Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116027, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116027, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116027, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116027, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116027, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116027, ChinaAberrant ubiquitination drives hepatocellular carcinoma (HCC) progression, yet the role of FBXO10—a key F-box E3 ubiquitin ligase component—remains uncharacterized. Through bioinformatics analyses and functional validation, we establish FBXO10 as a critical oncogenic driver in HCC. Transcriptomic data from public databases (TIMER, UALCAN, GEO) revealed significant FBXO10 upregulation in HCC tissues, with elevated expression predicting advanced tumor stage, metastasis, and reduced survival. Functionally, FBXO10 silencing suppressed HCC cell proliferation while its overexpression promoted tumor growth. Mechanistic studies revealed that FBXO10 directly interacts with FRMPD1 to mediate its K63-linked polyubiquitination and stabilization, independent of transcriptional regulation. FRMPD1 restoration rescued FBXO10-mediated proliferation, confirming its role as the key downstream effector. Clinically, FBXO10 expression correlated with TP53 mutations and adverse clinicopathological features. Our findings reveal a novel FBXO10–FRMPD1 axis promoting hepatocarcinogenesis through post-translational stabilization, positioning FBXO10 as both a prognostic biomarker and therapeutic target in HCC.https://www.mdpi.com/1467-3045/47/6/391hepatocarcinomaFBXO10FRMPD1ubiquitinationcell proliferation |
| spellingShingle | Wuguang Liu Bin Xu Kashif Kifayat Yuhong Xie Xiaolong Liu Chengyong Dong Liming Wang FBXO10 Drives Hepatocellular Carcinoma Proliferation via K63-Linked Ubiquitination and Stabilization of FRMPD1 Current Issues in Molecular Biology hepatocarcinoma FBXO10 FRMPD1 ubiquitination cell proliferation |
| title | FBXO10 Drives Hepatocellular Carcinoma Proliferation via K63-Linked Ubiquitination and Stabilization of FRMPD1 |
| title_full | FBXO10 Drives Hepatocellular Carcinoma Proliferation via K63-Linked Ubiquitination and Stabilization of FRMPD1 |
| title_fullStr | FBXO10 Drives Hepatocellular Carcinoma Proliferation via K63-Linked Ubiquitination and Stabilization of FRMPD1 |
| title_full_unstemmed | FBXO10 Drives Hepatocellular Carcinoma Proliferation via K63-Linked Ubiquitination and Stabilization of FRMPD1 |
| title_short | FBXO10 Drives Hepatocellular Carcinoma Proliferation via K63-Linked Ubiquitination and Stabilization of FRMPD1 |
| title_sort | fbxo10 drives hepatocellular carcinoma proliferation via k63 linked ubiquitination and stabilization of frmpd1 |
| topic | hepatocarcinoma FBXO10 FRMPD1 ubiquitination cell proliferation |
| url | https://www.mdpi.com/1467-3045/47/6/391 |
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