Loss of ACSL1 fuels ferroptosis resistance in clear cell renal carcinoma.

ABSTRACT:

Background

Clear cell renal cell carcinoma (ccRCC), the most common kidney cancer subtype, is marked by lipid metabolism reprogramming and therapy resistance. Ferroptosis-an iron-dependent, lipid peroxidation-driven cell death-has gained attention as a therapeutic strategy. This study investigates the role of ACSL1, a key lipid metabolism enzyme, in ccRCC.

Methods

Using TCGA/GEO datasets, qPCR, immunohistochemistry, and immunofluorescence, ACSL1 expression and clinical significance were analyzed. Functional assays with ACSL1-overexpressing ccRCC cells and a xenograft mouse model evaluated its impact on tumor behavior. Transcriptomics and lipidomics, alongside ROS, ferroptosis, and p53 inhibitors, were applied to uncover mechanisms.

Results

ACSL1 is markedly downregula

SUBMITTER: Wang S 

PROVIDER: S-EPMC12505508 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature