ArticleThe Journal of clinical investigation2021
Apobec1 complementation factor overexpression promotes hepatic steatosis, fibrosis, and hepatocellular cancer.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 54 citations in OpenAlex.
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- Review
- RNA editing: an emerging frontier in cancer therapy - explorations, opportunities, and challenges.International journal of surgery (London, England) · 2026Article
- Reprogramming tumor immunity through APOBEC3s-mediated mutagenesis: from genome instability to immune checkpoint interactions.Frontiers in immunology · 2026Review
- Integrated analysis of RNA-binding proteins in MAFLD: mechanistic insights and diagnostic biomarker potential via alternative splicing.Journal of bioenergetics and biomembranes · 2025Article
- Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.Protein & cell · 2025Review
- Glycolysis-Derived Lactate Induces ACSL4 Expression and Lactylation to Activate Ferroptosis during Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- The genomic legacy of selectively breeding rhesus macaques for HIV/AIDS-related research.bioRxiv : the preprint server for biology · 2025Article
- Deciphering the Oncogenic Landscape of Hepatocytes Through Integrated Single-Nucleus and Bulk RNA-Seq of Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Identification of Causal Plasma Proteins in Hepatocellular Carcinoma via Two-Sample Mendelian Randomization and Integrative Transcriptomic‒Proteomic Analysis.Cancer research communications · 2025Article
- T1/T2 mapping as a non-invasive method for evaluating liver fibrosis based on correlation of biomarkers: a preclinical study.BMC gastroenterology · 2025Article
- Spatial Transcriptome Mapping of the Desmoplastic Growth Pattern of Colorectal Liver Metastases by In Situ Sequencing Reveals a Biologically Relevant Zonation of the Desmoplastic Rim.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- The roles and mechanisms of coding and noncoding RNA variations in cancer.Experimental & molecular medicine · 2024Review
- Apolipoprotein E knockout, but not cholesteryl ester transfer protein (CETP)-associated high-density lipoprotein cholesterol (HDL-C) lowering, exacerbates muscle wasting in dysferlin-null mice.Lipids in health and disease · 2024Article
- Development and validation of prognostic signatures of NAD+ metabolism and immune-related genes in colorectal cancer.Heliyon · 2024Article
- Commensal microbiome dysbiosis elicits interleukin-8 signaling to drive fibrotic skin disease.PNAS nexus · 2024Article
- Signaling through the nicotinic acetylcholine receptor in the liver protects against the development of metabolic dysfunction-associated steatohepatitis.PLoS biology · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
The RNA-binding protein Apobec1 complementation factor (A1CF) regulates posttranscriptional ApoB mRNA editing, but the range of RNA targets and the long-term effect of altered A1CF expression on liver function are unknown. Here we studied hepatocyte-specific A1cf-transgenic (A1cf+/Tg), A1cf+/Tg Apobec1-/-, and A1cf-/- mice fed chow or high-fat/high-fructose diets using RNA-Seq, RNA CLIP-Seq, and tissue microarrays from human hepatocellular cancer (HCC). A1cf+/Tg mice exhibited increased hepatic proliferation and steatosis, with increased lipogenic gene expression (Mogat1, Mogat2, Cidea, Cd36) associated with shifts in polysomal RNA distribution. Aged A1cf+/Tg mice developed spontaneous fibrosis, dysplasia, and HCC, and this development was accelerated on a high-fat/high-fructose diet and was independent of Apobec1. RNA-Seq revealed increased expression of mRNAs involved in oxidative stress (Gstm3, Gpx3, Cbr3), inflammatory response (Il19, Cxcl14, Tnfα, Ly6c), extracellular matrix organization (Mmp2, Col1a1, Col4a1), and proliferation (Kif20a, Mcm2, Mcm4, Mcm6), and a subset of mRNAs (including Sox4, Sox9, Cdh1) were identified in RNA CLIP-Seq. Increased A1CF expression in human HCC correlated with advanced fibrosis and with reduced survival in a subset with nonalcoholic fatty liver disease. In conclusion, we show that hepatic A1CF overexpression selectively alters polysomal distribution and mRNA expression, promoting lipogenic, proliferative, and inflammatory pathways leading to HCC.
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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.