Loss of ESRP2 Activates TAK1-MAPK Signaling through the Fetal RNA-Splicing Program to Promote Hepatocellular Carcinoma Progression.

ABSTRACT: Tumors usually display fetal-like characteristics, and many oncofetal proteins have been identified. However, fetal-like reprogramming of RNA splicing in hepatocellular carcinoma (HCC) is poorly understood. Here, it is demonstrated that the expression of epithelial splicing regulatory protein 2 (ESRP2), an RNA splicing factor, is suppressed in fetal hepatocytes and HCC, in parallel with tumor progression. By combining RNA-Seq with splicing analysis, it is identified that ESRP2 controls the fetal-to-adult switch of multiple splice isoforms in HCC. Functionally, ESRP2 suppressed cell proliferation and migration by specifically switching the alternative splicing (AS) of the TAK1 gene and restraining the expression of the fetal and oncogenic isoform, TAK1_ΔE12. Notably, aberrant TAK1 splicing

SUBMITTER: Yan Q 

PROVIDER: S-EPMC10767434 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature