ACAD8-mediated valine catabolism inhibits mTOR signaling to suppress lipid accumulation and progression of clear cell renal cell carcinoma

Abstract

Highlights • WGCNA identified a lipid and branched-chain amino acid metabolism–related module closely associated with ccRCC clinical features.• ACAD8 was identified as a key gene downregulated in ccRCC, with low expression predicting poor prognosis.• ACAD8 suppressed ccRCC proliferation, migration, invasion, and lipid accumulation both in vitro and in vivo.• Mechanistically, ACAD8 promoted valine degradation, thereby inhibiting mTOR/SREBP1 signaling and lipogenesis.• Valine supplementation reversed the tumor-suppressive effects of ACAD8, confirming a valine-dependent regulatory mechanism.