Identification of RAD51AP1 as a key gene in hepatitis B virus-associated hepatocellular carcinoma
Background: Hepatocellular carcinoma (HCC) is a significant global health concern, with chronic hepatitis B virus (HBV) infection being a major contributor. Understanding the mechanisms of HBV-associated HCC is crucial to improving the prognosis and developing effective treatments. Methods: HBV-asso...
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Elsevier
2025-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024176256 |
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| author | Meiling Wan Yonghong Wang Xiaoling Liu Yaling Li Cunliang Deng Changfeng Sun |
| author_facet | Meiling Wan Yonghong Wang Xiaoling Liu Yaling Li Cunliang Deng Changfeng Sun |
| author_sort | Meiling Wan |
| collection | DOAJ |
| description | Background: Hepatocellular carcinoma (HCC) is a significant global health concern, with chronic hepatitis B virus (HBV) infection being a major contributor. Understanding the mechanisms of HBV-associated HCC is crucial to improving the prognosis and developing effective treatments. Methods: HBV-associated HCC datasets (GSE19665, GSE121248, GSE55092, GSE94660, and TCGA-LIHC) acquired from public databases were mined to identify key driver genes by differentially expressed gene analysis, weighted gene co-expression network analysis (WGCNA), followed by protein-protein interaction network analysis, Lasso-Cox regression analysis, and randomforestSRC algorithm. Then, in vitro experiments including CCK-8 assay, wound healing, and Transwell assay were performed to explore the functions and mechanisms. Results: RAD51AP1 was identified as a specific key gene linked to the progression of HBV-associated HCC. High expression of RAD51AP1 was associated with worse overall survival (OS) in patients with HBV-associated HCC, but not in patients with non-HBV-associated HCC. Mechanistically, RAD51AP1 forms a potential ceRNA axis with LINC01419 and miR-8070, where LINC01419 acts as a molecular sponge for miR-8070 to upregulate RAD51AP1. HBV infection can enhance the LINC01419/miR-8070/RAD51AP1 axis, and LINC01419 overexpression conversely promotes HBV replication. The ceRNA axis and HBV synergistically promote the proliferation and metastasis of HBV-associated HCC cells. Furthermore, LINC01419 or RAD51AP1 knockdown, and miR-8070 overexpression in HepG2.2.15 cells significantly attenuated the Wnt/β-catenin signaling. Conclusions: The LINC01419/miR-8070/RAD51AP1 axis promotes the HBV-associated HCC progression through an HBV-boosted positive feedback loop and Wnt/β-catenin signaling. These findings provide novel insights into the underlying mechanisms and may offer potential diagnostic and therapeutic targets in HBV-associated HCC. |
| format | Article |
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| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-aaa592e8bb9a48beaaa238f73b8e15942025-01-17T04:51:43ZengElsevierHeliyon2405-84402025-01-01111e41594Identification of RAD51AP1 as a key gene in hepatitis B virus-associated hepatocellular carcinomaMeiling Wan0Yonghong Wang1Xiaoling Liu2Yaling Li3Cunliang Deng4Changfeng Sun5Department of Infectious Diseases, Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Laboratory of Infection and Immunity, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, ChinaDepartment of Infectious Diseases, Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Laboratory of Infection and Immunity, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, ChinaDepartment of Infectious Diseases, Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Laboratory of Infection and Immunity, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, ChinaDepartment of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, ChinaDepartment of Infectious Diseases, Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Laboratory of Infection and Immunity, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Corresponding author. Department of Infectious Diseases, Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China.Department of Infectious Diseases, Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Laboratory of Infection and Immunity, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Corresponding author. Department of Infectious Diseases, Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China.Background: Hepatocellular carcinoma (HCC) is a significant global health concern, with chronic hepatitis B virus (HBV) infection being a major contributor. Understanding the mechanisms of HBV-associated HCC is crucial to improving the prognosis and developing effective treatments. Methods: HBV-associated HCC datasets (GSE19665, GSE121248, GSE55092, GSE94660, and TCGA-LIHC) acquired from public databases were mined to identify key driver genes by differentially expressed gene analysis, weighted gene co-expression network analysis (WGCNA), followed by protein-protein interaction network analysis, Lasso-Cox regression analysis, and randomforestSRC algorithm. Then, in vitro experiments including CCK-8 assay, wound healing, and Transwell assay were performed to explore the functions and mechanisms. Results: RAD51AP1 was identified as a specific key gene linked to the progression of HBV-associated HCC. High expression of RAD51AP1 was associated with worse overall survival (OS) in patients with HBV-associated HCC, but not in patients with non-HBV-associated HCC. Mechanistically, RAD51AP1 forms a potential ceRNA axis with LINC01419 and miR-8070, where LINC01419 acts as a molecular sponge for miR-8070 to upregulate RAD51AP1. HBV infection can enhance the LINC01419/miR-8070/RAD51AP1 axis, and LINC01419 overexpression conversely promotes HBV replication. The ceRNA axis and HBV synergistically promote the proliferation and metastasis of HBV-associated HCC cells. Furthermore, LINC01419 or RAD51AP1 knockdown, and miR-8070 overexpression in HepG2.2.15 cells significantly attenuated the Wnt/β-catenin signaling. Conclusions: The LINC01419/miR-8070/RAD51AP1 axis promotes the HBV-associated HCC progression through an HBV-boosted positive feedback loop and Wnt/β-catenin signaling. These findings provide novel insights into the underlying mechanisms and may offer potential diagnostic and therapeutic targets in HBV-associated HCC.http://www.sciencedirect.com/science/article/pii/S2405844024176256RAD51AP1HBV-Associated HCCPrognostic biomarkerProliferationMetastasis |
| spellingShingle | Meiling Wan Yonghong Wang Xiaoling Liu Yaling Li Cunliang Deng Changfeng Sun Identification of RAD51AP1 as a key gene in hepatitis B virus-associated hepatocellular carcinoma Heliyon RAD51AP1 HBV-Associated HCC Prognostic biomarker Proliferation Metastasis |
| title | Identification of RAD51AP1 as a key gene in hepatitis B virus-associated hepatocellular carcinoma |
| title_full | Identification of RAD51AP1 as a key gene in hepatitis B virus-associated hepatocellular carcinoma |
| title_fullStr | Identification of RAD51AP1 as a key gene in hepatitis B virus-associated hepatocellular carcinoma |
| title_full_unstemmed | Identification of RAD51AP1 as a key gene in hepatitis B virus-associated hepatocellular carcinoma |
| title_short | Identification of RAD51AP1 as a key gene in hepatitis B virus-associated hepatocellular carcinoma |
| title_sort | identification of rad51ap1 as a key gene in hepatitis b virus associated hepatocellular carcinoma |
| topic | RAD51AP1 HBV-Associated HCC Prognostic biomarker Proliferation Metastasis |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024176256 |
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