| Autor: |
Tatsuo Kido, Yun-Fai Chris Lau |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Oncogenesis, Vol 12, Iss 1, Pp 1-9 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2157-9024 |
| DOI: |
10.1038/s41389-023-00449-3 |
| Popis: |
Abstract Androgen receptor variant 7 (AR-V7), an AR isoform with a truncated ligand-binding domain, functions as a transcription factor in an androgen-independent manner. AR-V7 is expressed in a subpopulation of hepatocellular carcinoma (HCC), however, its role(s) in this cancer is undefined. In this study, we investigated the potential roles of AR-V7 in hepatocarcinogenesis in vivo in a c-MYC-driven mouse HCC model generated by the hydrodynamic tail-vein injection system. The impacts of AR-V7 on gene expression in mouse HCC were elucidated by RNA-seq transcriptome and ontology analyses. The results showed that AR-V7 significantly exacerbated the c-MYC-mediated oncogenesis in the livers of both sexes. The transcriptome and bioinformatics analyses revealed that AR-V7 and c-MYC synergistically altered the gene sets involved in various cancer-related biological processes, particularly in lipid and steroid/sterol metabolisms. Importantly, AR-V7 suppressed a tumor suppressor Claudin 7 expression, upregulated by c-MYC overexpression via the p53 signaling pathway. Claudin 7 overexpression significantly suppressed the c-MYC-driven HCC development under p53-deficient conditions. Our results suggest that the AR-V7 exacerbates the c-MYC-driven hepatocarcinogenesis by potentiating the oncogenic roles and minimizing the anti-oncogenic functions of c-MYC. Since AR-V7 is expressed in a subpopulation of HCC cases, it could contribute to the inter- and intra-heterogeneity of HCC. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
|
Nepřihlášeným uživatelům se plný text nezobrazuje |
K zobrazení výsledku je třeba se přihlásit.
|
