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000304510 1001_ $$aCrouchet, Emilie$$b0
000304510 245__ $$aTargeting peroxiredoxin 2 prevents hepatocarcinogenesis in metabolic liver disease models.
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000304510 520__ $$aTreatment 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.
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000304510 650_7 $$2Other$$aCarbohydrate metabolism
000304510 650_7 $$2Other$$aHepatology
000304510 650_7 $$2Other$$aOncology
000304510 650_7 $$2Other$$aPreventative medicine
000304510 650_7 $$2Other$$aTherapeutics
000304510 7001_ $$aSchaeffer, Eugénie$$b1
000304510 7001_ $$aOudot, Marine A$$b2
000304510 7001_ $$aMoehlin, Julien$$b3
000304510 7001_ $$aGadenne, Cloé$$b4
000304510 7001_ $$aJühling, Frank$$b5
000304510 7001_ $$aEl Saghire, Hussein$$b6
000304510 7001_ $$aFujiwara, Naoto$$b7
000304510 7001_ $$aZhu, Shijia$$b8
000304510 7001_ $$aAkter Rasha, Fahmida$$b9
000304510 7001_ $$aDurand, Sarah C$$b10
000304510 7001_ $$aCharlot, Anouk$$b11
000304510 7001_ $$aPonsolles, Clara$$b12
000304510 7001_ $$aMartin, Romain$$b13
000304510 7001_ $$aBrignon, Nicolas$$b14
000304510 7001_ $$aDel Zompo, Fabio$$b15
000304510 7001_ $$aMeiss Heydmann, Laura$$b16
000304510 7001_ $$aParnot, Marie$$b17
000304510 7001_ $$aHamdane, Nourdine$$b18
000304510 7001_ $$0P:(DE-He78)92c93319837b4b915db8393795faf0b6$$aHeide, Danijela$$b19$$udkfz
000304510 7001_ $$0P:(DE-He78)9c964482bd7f3f66d88f99962e175f39$$aHetzer, Jenny$$b20$$udkfz
000304510 7001_ $$0P:(DE-He78)66ed2d4ec9bc11d29b87ac006adf85e5$$aHeikenwälder, Mathias$$b21$$udkfz
000304510 7001_ $$aFelli, Emanuele$$b22
000304510 7001_ $$aPessaux, Patrick$$b23
000304510 7001_ $$aPochet, Nathalie$$b24
000304510 7001_ $$aZoll, Joffrey$$b25
000304510 7001_ $$aCunniff, Brian$$b26
000304510 7001_ $$aHoshida, Yujin$$b27
000304510 7001_ $$aMailly, Laurent$$b28
000304510 7001_ $$aBaumert, Thomas F$$b29
000304510 7001_ $$aSchuster, Catherine$$b30
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