ArticleJournal of hepatology2021
Dysregulation of the ESRP2-NF2-YAP/TAZ axis promotes hepatobiliary carcinogenesis in non-alcoholic fatty liver disease.
Article in Journal of hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Decoding the role of aberrant RNA alternative splicing in hepatocellular carcinoma: a comprehensive review.Journal of cancer research and clinical oncology · 2023Pooled it
- Association Between Allostatic Load, Genetic Susceptibility, and Liver Cancer Incidence: A Large-Scale Prospective Cohort Study.International journal of cancer · 2026Article
- Circular RNA Circ_0020236 Inhibits Hepatocellular Carcinoma Cell Proliferation and Migration Through Modulating the MiR-1825/IKBKB Axis.Biochemical genetics · 2026Article
- ZFP36 Alleviates MASLD Through Facilitating TEAD4 mRNA Degradation After Sleeve Gastrectomy.International journal of molecular sciences · 2026Article
- The dual role of OTUD3 in cancer: mechanisms and therapeutic implications.Cancer cell international · 2025Review
- Research and development prospects of TRIM65.Journal of cancer research and clinical oncology · 2025Review
- ESRP2-microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation.Genes & development · 2025Article
- Review
- Regulatory roles of RNA binding proteins in the Hippo pathway.Cell death discovery · 2025Review
- Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence.NPJ precision oncology · 2025Article
- Regulation of Hippo-YAP1/TAZ pathway in metabolic dysfunction-associated steatotic liver disease.Frontiers in pharmacology · 2025Review
- YAP/TAZ as master regulators in liver regeneration and disease: insights into mechanisms and therapeutic targets.Molecular biology reports · 2024Review
- Mechanistic Insights into Alternative Gene Splicing in Oxidative Stress and Tissue Injury.Antioxidants & redox signaling · 2024Review
- Review
- TRIM65/NF2/YAP1 Signaling Coordinately Orchestrates Metabolic and Immune Advantages in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The histone lysine acetyltransferase KAT2B inhibits cholangiocarcinoma growth: evidence for interaction with SP1 to regulate NF2-YAP signaling.Journal of experimental & clinical cancer research : CR · 2024Article
- Alternative splicing and related RNA binding proteins in human health and disease.Signal transduction and targeted therapy · 2024Review
- Dysregulation of RNA splicing in early non-alcoholic fatty liver disease through hepatocellular carcinoma.Scientific reports · 2024Article
- 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
- Complex roles of Hippo-YAP/TAZ signaling in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsNon-alcoholic fatty liver disease (NAFLD), the hepatic correlate of the metabolic syndrome, is a major risk factor for hepatobiliary cancer (HBC). Although chronic inflammation is thought to be the root cause of all these diseases, the mechanism whereby it promotes HBC in NAFLD remains poorly understood. Herein, we aim to evaluate the hypothesis that inflammation-related dysregulation of the ESRP2-NF2-YAP/TAZ axis promotes HB carcinogenesis.
methodsWe use murine NAFLD models, liver biopsies from patients with NAFLD, human liver cancer registry data, and studies in liver cancer cell lines.
resultsOur results confirm the hypothesis that inflammation-related dysregulation of the ESRP2-NF2-YAP/TAZ axis promotes HB carcinogenesis, supporting a model whereby chronic inflammation suppresses hepatocyte expression of ESRP2, an RNA splicing factor that directly targets and activates NF2, a tumor suppressor that is necessary to constrain YAP/TAZ activation. The resultant loss of NF2 function permits sustained YAP/TAZ activity that drives hepatocyte proliferation and de-differentiation.
conclusionHerein, we report on a novel mechanism by which chronic inflammation leads to sustained activation of YAP/TAZ activity; this imposes a selection pressure that favors liver cells with mutations enabling survival during chronic oncogenic stress. LAY SUMMARY: Non-alcoholic fatty liver disease (NAFLD) increases the risk of hepatobiliary carcinogenesis. However, the underlying mechanism remains unknown. Our study demonstrates that chronic inflammation suppresses hepatocyte expression of ESRP2, an adult RNA splicing factor that activates NF2. Thus, inactive (fetal) NF2 loses the ability to activate Hippo kinases, leading to the increased activity of downstream YAP/TAZ and promoting hepatobiliary carcinogenesis in chronically injured livers.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.