TY  - JOUR
AU  - Crouchet, Emilie
AU  - Schaeffer, Eugénie
AU  - Oudot, Marine A
AU  - Moehlin, Julien
AU  - Gadenne, Cloé
AU  - Jühling, Frank
AU  - El Saghire, Hussein
AU  - Fujiwara, Naoto
AU  - Zhu, Shijia
AU  - Akter Rasha, Fahmida
AU  - Durand, Sarah C
AU  - Charlot, Anouk
AU  - Ponsolles, Clara
AU  - Martin, Romain
AU  - Brignon, Nicolas
AU  - Del Zompo, Fabio
AU  - Meiss Heydmann, Laura
AU  - Parnot, Marie
AU  - Hamdane, Nourdine
AU  - Heide, Danijela
AU  - Hetzer, Jenny
AU  - Heikenwälder, Mathias
AU  - Felli, Emanuele
AU  - Pessaux, Patrick
AU  - Pochet, Nathalie
AU  - Zoll, Joffrey
AU  - Cunniff, Brian
AU  - Hoshida, Yujin
AU  - Mailly, Laurent
AU  - Baumert, Thomas F
AU  - Schuster, Catherine
TI  - Targeting peroxiredoxin 2 prevents hepatocarcinogenesis in metabolic liver disease models.
JO  - The journal of clinical investigation
VL  - 135
IS  - 21
SN  - 0021-9738
CY  - Ann Arbor, Mich.
PB  - ASCJ
M1  - DKFZ-2025-01898
SP  - e169395
PY  - 2025
N1  - 2025 Sep 11;135(21):e169395
AB  - Treatment options for advanced liver disease and hepatocellular carcinoma (HCC) are limited and strategies to prevent HCC development are lacking. Aiming to discover novel therapeutic targets, we combined genome wide transcriptomic analysis of liver tissues from patients with advanced liver disease and HCC and a cell-based system predicting liver disease progression and HCC risk. Computational analysis predicted peroxiredoxin 2 (PRDX2) as a candidate gene mediating hepatocarcinogenesis and HCC risk. Analysis of HCC patient tissues confirmed a perturbed expression of PRDX2 in cancer. In vivo perturbation studies in mouse models for MASH driven hepatocarcinogenesis showed that specific Prdx2 knockout in hepatocytes significantly improved metabolic liver functions, restored AMPK activity and prevented HCC development by suppressing oncogenic signaling. Perturbations studies in HCC cell lines, a CDX mouse model and patient-derived HCC spheroids unraveled that PRDX2 also mediates cancer initiation, cancer cell proliferation and survival through its antioxidant activity. Targeting PRDX2 may therefore be a valuable strategy to prevent HCC development in metabolic liver disease.
KW  - Carbohydrate metabolism (Other)
KW  - Hepatology (Other)
KW  - Oncology (Other)
KW  - Preventative medicine (Other)
KW  - Therapeutics (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40932790
DO  - DOI:10.1172/JCI169395
UR  - https://inrepo02.dkfz.de/record/304510
ER  -