ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Loss of ESRP2 Activates TAK1-MAPK Signaling through the Fetal RNA-Splicing Program to Promote Hepatocellular Carcinoma Progression.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Circular RNA Circ_0020236 Inhibits Hepatocellular Carcinoma Cell Proliferation and Migration Through Modulating the MiR-1825/IKBKB Axis.Biochemical genetics · 2026Article
- FXR1-Directed Alternative Splicing of MK5 Drives Hepatocellular Carcinoma Progression by Activating GSK3β Signaling.Cancer science · 2026Article
- Oncofetal reprogramming in hepatocellular carcinoma: linking developmental programs to cancer vaccines and immunotherapy.Clinical and molecular hepatology · 2026Review
- ESRP2 constrains EMT plasticity associated with ZEB1 expression in bladder cancer.Frontiers in oncology · 2026Article
- TPD52 promotes the proliferation and metastasis of gastric cancer cells.BMC gastroenterology · 2025Article
- Targeting phase separation: a promising treatment option for hepatocellular carcinoma.Cell communication and signaling : CCS · 2025Review
- Overexpression pattern, function, and clinical value of proteasome 26S subunit non-ATPase 6 in hepatocellular carcinoma.World journal of clinical oncology · 2025Article
- Podocyte OTUD5 alleviates diabetic kidney disease through deubiquitinating TAK1 and reducing podocyte inflammation and injury.Nature communications · 2024Article
- Role of ADAR1 on Proliferation and Differentiation in Porcine Preadipocytes.Animals : an open access journal from MDPI · 2024Article
- Liquid-liquid phase separation in hepatocellular carcinoma.Frontiers in cell and developmental biology · 2024Review
- Loss of ESRP2 Activates TAK1-MAPK Signaling through the Fetal RNA-Splicing Program to Promote Hepatocellular Carcinoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
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 led to the activation of p38MAPK signaling and predicted poor prognosis in HCC patients. Further investigation revealed that TAK1_ΔE12 protein interacted closely with TAB3 and formed liquid condensation in HCC cells, resulting in p38MAPK activation, enhanced cell migration, and accelerated tumorigenesis. Loss of ESRP2 sensitized HCC cells to TAK1 kinase inhibitor (TAK1i), promoting pyroptotic cell death and CD8+ T cell infiltration. Combining TAK1i with immune checkpoint therapy achieved potent tumor regression in mice. Overall, the findings reveal a previously unexplored onco-fetal reprogramming of RNA splicing and provide novel therapeutic avenues for HCC.
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