Targeting the MIR4435-2HG/miR-29c-3p/FSP1 axis overcomes lenvatinib resistance by inducing ferroptosis in hepatocellular carcinoma.

ABSTRACT:

Background

Lenvatinib resistance is a major clinical challenge in advanced hepatocellular carcinoma (HCC). While ferroptosis has emerged as a promising target to overcome therapy resistance, the mechanistic link between ferroptosis and lenvatinib resistance in HCC remains incompletely understood.

Methods

We analyzed clinical data from TCGA-LIHC and performed functional assays in two HCC cell lines. RNA antisense purification sequencing (RAP-seq) was used to identify downstream targets, and the mechanisms were validated by dual-luciferase reporter assays and Western blotting. Ferroptosis was assessed by measuring lipid reactive oxygen species (lipid ROS) and labile iron levels. Therapeutic efficacy was evaluated both in vitro and in vivo.

Results

MIR4435-2HG was upregu

SUBMITTER: Zhang C 

PROVIDER: S-EPMC12849258 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature