biostudies-literatureZhou DNatural Science Foundation of Zhejiang ProvinceNational Natural Science Foundation of ChinaShanghai Municipal Health Bureau110904https://www.ebi.ac.uk/biostudies/studies/S-EPMC12702014biostudies-literatureUnknown301(12)Growing evidence indicates that the cellular senescence (CS) plays a crucial role in hepatocarcinogenesis. Transmembrane BCL-2-associated X protein inhibitor motif containing 1 (TMBIM1) has been shown to inhibit CS. However, the role and mechanism of TMBIM1 associated CS in hepatocarcinogenesis remains unclear. In our study, TMBIM1 was highly expressed in the adjacent tissues of patients with liver cancer and its expression of TMBIM1 gradually decreased during hepatocarcinogenesis in a rat primary liver cancer model. In a Tmbim1-overexpressed rat model, the occurrence of hepatocellular carcinoma (HCC) was highly inhibited and overall survival was prolonged. In addition, the aggregation of senescent cells promotes the activation of hepatic progenitor cells to promote the occurrence of HCC. The Journal of biological chemistryTransmembrane BAX inhibitor motif containing 1 inhibition of lysosomal degradation of TGF-β receptor 1 suppresses cellular senescence and hepatocarcinogenesis.PMC12702014820730378220323720214Y0013LQ23H16004982472997821732768207303282472928823029152024ZZ2006Jiang JZheng YDuan LZhang KZhang HZhang LHou XLiu WQian XZhou DYu WZhu XXue MFeng SWei LfalseTransmembrane BAX inhibitor motif containing 1 inhibition of lysosomal degradation of TGF-β receptor 1 suppresses cellular senescence and hepatocarcinogenesis.Growing evidence indicates that the cellular senescence (CS) plays a crucial role in hepatocarcinogenesis. Transmembrane BCL-2-associated X protein inhibitor motif containing 1 (TMBIM1) has been shown to inhibit CS. However, the role and mechanism of TMBIM1 associated CS in hepatocarcinogenesis remains unclear. In our study, TMBIM1 was highly expressed in the adjacent tissues of patients with liver cancer and its expression of TMBIM1 gradually decreased during hepatocarcinogenesis in a rat primary liver cancer model. In a Tmbim1-overexpressed rat model, the occurrence of hepatocellular carcinoma (HCC) was highly inhibited and overall survival was prolonged. In addition, the aggregation of senescent cells promotes the activation of hepatic progenitor cells to promote the occurrence of HCC. 2025-01-01T00:00:00Z2025 Dec2026-07-15T11:17:10.353Z2026-07-04T03:12:02.161ZS-EPMC127020144119772010.1016/j.jbc.2025.110904