biostudies-literatureLi MThe Open Fund for Scientific Research of Jiangxi Cancer HospitalNational Natural Science Foundation of ChinaThe “Five-level Progressive” talent cultivation project of Jiangxi Cancer Hospital & Institute2574988https://www.ebi.ac.uk/biostudies/studies/S-EPMC12541920biostudies-literatureUnknown40(1)HCC is a highly lethal cancer characterised by significant sorafenib resistance, leading to poor patient outcomes. Recent studies have suggested that MED8 plays a role in enhancing tumour resistance to drugs, but its role in drug resistance in HCC has not yet been reported. This study found significantly higher MED8 expression in HCC tissues compared to adjacent noncancerous tissues. Increased MED8 expression in HCC correlates with poorer overall survival. Functional assays demonstrated that reduced MED8 expression inhibited HCC cell proliferation and epithelial-mesenchymal transition, promoted apoptosis, and increased sensitivity to sorafenib. Overexpression of MED8 elevated TRIP4 protein levels. TRIP4 overexpression negated the effects of MED8 knockdown, whereas TRIP4 suppression inhibitJournal of enzyme inhibition and medicinal chemistryTargeting MED8 enhances sorafenib sensitivity in hepatocellular carcinoma by disrupting epithelial-mesenchymal transition mechanisms.PMC125419202021J1282260467WCDJ2024YQ05Yuan TLiang SLi JJin AHe JTu QYi BYou XMao LZhou XLi MXu ZfalseTargeting MED8 enhances sorafenib sensitivity in hepatocellular carcinoma by disrupting epithelial-mesenchymal transition mechanisms.HCC is a highly lethal cancer characterised by significant sorafenib resistance, leading to poor patient outcomes. Recent studies have suggested that MED8 plays a role in enhancing tumour resistance to drugs, but its role in drug resistance in HCC has not yet been reported. This study found significantly higher MED8 expression in HCC tissues compared to adjacent noncancerous tissues. Increased MED8 expression in HCC correlates with poorer overall survival. Functional assays demonstrated that reduced MED8 expression inhibited HCC cell proliferation and epithelial-mesenchymal transition, promoted apoptosis, and increased sensitivity to sorafenib. Overexpression of MED8 elevated TRIP4 protein levels. TRIP4 overexpression negated the effects of MED8 knockdown, whereas TRIP4 suppression inhibit2025-01-01T00:00:00Z2025 Dec2026-06-04T16:15:55.181Z2026-05-13T14:24:35.435ZS-EPMC125419204111731110.1080/14756366.2025.2574988