Targeting TIMM23 to overcome osteosarcoma chemoresistance.

ABSTRACT: Osteosarcoma (OS) is a malignant tumor whose chemoresistance severely compromises therapeutic efficacy. This study aims to investigate the molecular mechanism by which TIMM23 mediates M2 polarization of macrophages through mitophagy and regulates TIMM23-PARGP1 fusion gene expression and chemoresistance in OS. Single-cell transcriptomic analysis revealed a strong interaction between macrophages and tumor cells. By integrating bulk RNA sequencing data and weighted gene co-expression network analysis (WGCNA) co-expression network analysis, we identified TIMM23 as a key gene associated with macrophage polarization. Using STAR-Fusion, we further detected the TIMM23-PARGP1 fusion gene, which was validated via fluorescence in situ hybridization (FISH). CRISPR/Cas9 was employed to generate TIMM23-

SUBMITTER: Tao Z 

PROVIDER: S-EPMC12644526 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature