Other
13 Authors
- Komakula SSB,
- Chen W,
- Athavale D,
- Nieto N,
- Ge X,
- Lantvit D,
- Das S,
- Gao S,
- Guzman G,
- Han H,
- Song Z,
- Barahona I,
- Desert R
| First Author | Athavale D | Year | 2023 |
| Journal | Hepatol Commun | Volume | 7 |
| Issue | 12 | PubMed ID | 38055645 |
| Mgi Jnum | J:354052 | Mgi Id | MGI:7719071 |
| Doi | 10.1097/HC9.0000000000000311 | Citation | Athavale D, et al. (2023) Overexpression of HMGB1 in hepatocytes accelerates PTEN inactivation-induced liver cancer. Hepatol Commun 7(12) |
| abstractText | BACKGROUND: Liver cancer is increasing due to the rise in metabolic dysfunction-associated steatohepatitis (MASH). High-mobility group box-1 (HMGB1) is involved in the pathogenesis of chronic liver disease, but its role in MASH-associated liver cancer is unknown. We hypothesized that an increase in hepatocyte-derived HMGB1 in a mouse model of inactivation of PTEN that causes MASH could promote MASH-induced tumorigenesis. METHODS: We analyzed publicly available transcriptomics datasets, and to explore the effect of overexpressing HMGB1 in cancer progression, we injected 1.5-month-old PtenHep mice with adeno-associated virus serotype-8 (AAV8) vectors to overexpress HMGB1-EGFP or EGFP, and sacrificed them at 3, 9 and 11 months of age. RESULTS: We found that HMGB1 mRNA increases in human MASH and MASH-induced hepatocellular carcinoma (MASH-HCC) compared to healthy livers. Male and female PtenHep mice overexpressing HMGB1 showed accelerated liver tumor development at 9 and 11 months, respectively, with increased tumor size and volume, compared to control PtenHep mice. Moreover, PtenHep mice overexpressing HMGB1, had increased incidence of mixed HCC-intrahepatic cholangiocarcinoma (iCCA). All iCCAs were positive for nuclear YAP and SOX9. Male PtenHep mice overexpressing HMGB1 showed increased cell proliferation and F4/80+ cells at 3 and 9 months. CONCLUSION: Overexpression of HMGB1 in hepatocytes accelerates liver tumorigenesis in PtenHep mice, enhancing cell proliferation and F4/80+ cells to drive MASH-induced liver cancer. |
