HIF-2α/LPCAT1 orchestrates the reprogramming of lipid metabolism in ccRCC by modulating the FBXW7-mediated ubiquitination of ACLY.

ABSTRACT: The current research revealed a strong link between lipid reprogramming and dysregulated lipid metabolism to the genesis and development of clear cell renal cell carcinoma (ccRCC). Pathologically, ccRCC exhibits a high concentration of lipid droplets within the cytoplasm. HIF-2α expression has previously been demonstrated to be elevated in ccRCC caused by mutations in the von Hippel-Lindau (VHL) gene, which plays a vital role in the development of renal cell carcinoma. Nevertheless, the mechanisms by which HIF-2α influences lipid metabolism reprogramming are unknown. Our investigation demonstrated that HIF-2α directly binds to the promoter region of LPCAT1, promoting its transcription. RNA-seq and lipidomics mass spectrometry studies showed that knocking down LPCAT1 significantly reduced t

SUBMITTER: Fei M 

PROVIDER: S-EPMC11705634 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature