Low miR-936-mediated upregulation of Pim-3 drives sorafenib resistance in liver cancer through ferroptosis inhibition by activating the ANKRD18A/Src/NRF2 pathway.

ABSTRACT:

Objective

Sorafenib, a multikinase inhibitor, is currently the standard treatment for advanced liver cancer. However, its application has become limited by the development of drug resistance. We intended to explore the mechanisms underlying the development of sorafenib resistance, therefore identifying an effective strategy to overcome sorafenib resistance remain challenges.

Methods

Here, the follow-up of liver cancer patients undergoing sorafenib therapy, as well as animal tumor challenge and treatment were performed. The sorafenib-resistant liver cancer cell lines Huh7/SOR and HepG2/SOR were also established. miRNA and mRNA microarray analyses, TargetScan prediction, dual luciferase reporter assay, RNA pull-down assay, co-mmunoprecipitation (Co-IP) and pull-down assays, a

SUBMITTER: Li X 

PROVIDER: S-EPMC11540556 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature