Transcriptomics

Dataset Information

0

Hepatitis B/C viruses manipulate TNNT1 expression to induce epithelial-mesenchymal transition and hepatocellular carcinogenesis


ABSTRACT: Infection with hepatitis B and C viruses (HBV and HCV) is a major cause of hepatocellular carcinoma (HCC). While troponin T (TNNT1) is essential for actin thin filament function, little is known about its role in HBV/HCV-associated HCC. Here, we found TNNT1 expression was significantly upregulated in HBV/HCV-infected hepatoma cells, HCC tissues, and mouse models. HBV/HCV-induced c-Myc acts as a transcription factor for TNNT1 induction. HBV/HCV-induced TNNT1 binds metastasis-associated protein 2 (MTA2) and activates the PI3K-AKT-mTOR-TNNT1 loop, causing lysosomal dysfunction and autophagy suppression. This leads to increased proliferation and epithelial-mesenchymal transition (EMT) of liver cancer cells marked by Vimentin and ZEB2. Four amino acid residues (R110A, E112A, R115A, and E119A) within the TNNT1 troponin domain are required for TNNT1-MTA2 binding and mediate TNNT1’s suppression of autophagy and promotion of proliferation/EMT. Importantly, liver-specific TNNT1 deficiency in mice attenuates HBV/HCV-induced c-Myc-driven HCC EMT properties in vivo. This study reveals for the first time that hepatitis virus-induced TNNT1 can induce EMT and hepatocellular carcinogenesis. TNNT1 may be a promising target for viral HCC therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE233441 | GEO | 2023/11/21

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2010-04-10 | E-GEOD-21279 | biostudies-arrayexpress
2010-07-06 | E-GEOD-19665 | biostudies-arrayexpress
2010-04-10 | GSE21279 | GEO
2013-11-14 | E-GEOD-44074 | biostudies-arrayexpress
2010-07-06 | GSE19665 | GEO
2013-02-20 | E-GEOD-40744 | biostudies-arrayexpress
2014-09-16 | E-GEOD-60753 | biostudies-arrayexpress
2013-11-14 | GSE44074 | GEO
| phs000509 | dbGaP
2024-06-29 | PXD053504 | JPOST Repository