ArticleClinical and translational medicine2022
Spliceosomal profiling identifies EIF4A3 as a novel oncogene in hepatocellular carcinoma acting through the modulation of FGFR4 splicing.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Intermittent time-restricted feeding recapitulates the physiological benefits of daily time-restricted feeding in male mice with chronic metabolic disease.Molecular metabolism · 2026Article
- Article
- An Integrative RNA Spliceosomic Landscape of Pancreatic Neuroendocrine Tumors Identifies Clinically Relevant Molecular Subgroups.Endocrine pathology · 2026Article
- Impaired splicing machinery in craniopharyngiomas unveils PRPF8 and RAVER1 as novel biomarkers and therapeutic targets.Acta neuropathologica communications · 2025Article
- EIF4A3-Mediated downregulation of circPTEN promotes hepatocellular carcinoma progression through the miR-1289/RBM38 Axis.Journal of molecular histology · 2025Article
- Quantitative proteomic analysis unveils a critical role of VARS1 in hepatocellular carcinoma aggressiveness through the modulation of MAGI1 expression.Molecular cancer · 2025Article
- Specificity of mRNA binding to proteins within the NMD machinery is influenced in cancer.Frontiers in molecular biosciences · 2025Article
- The splicing machinery is dysregulated and represents a therapeutic vulnerability in breast cancer.Cellular and molecular life sciences : CMLS · 2024Article
- The crosstalk between alternative splicing and circular RNA in cancer: pathogenic insights and therapeutic implications.Cellular & molecular biology letters · 2024Review
- The oncogenic role of EIF4A3/CDC20 axis in the endometrial cancer.Journal of molecular medicine (Berlin, Germany) · 2024Article
- The Exon Junction Complex component EIF4A3 plays a splicing-linked oncogenic role in pancreatic ductal adenocarcinoma.Cancer gene therapy · 2024Article
- Splicing Machinery Is Impaired in Oral Squamous Cell Carcinomas and Linked to Key Pathophysiological Features.International journal of molecular sciences · 2024Article
- Proteomics Identifies LUC7L3 as a Prognostic Biomarker for Hepatocellular Carcinoma.Current issues in molecular biology · 2024Article
- Article
- Comprehensive analysis identifies long non-coding RNA RNASEH1-AS1 as a potential prognostic biomarker and oncogenic target in hepatocellular carcinoma.American journal of cancer research · 2024Article
- Altered splicing machinery in lung carcinoids unveils NOVA1, PRPF8 and SRSF10 as novel candidates to understand tumor biology and expand biomarker discovery.Journal of translational medicine · 2023Article
- A Novel Prognostic Signature of comprising Nine NK Cell signatures Based on Both Bulk RNA Sequencing and Single-Cell RNA Sequencing for Hepatocellular Carcinoma.Journal of Cancer · 2023Article
- Spliceosomal profiling identifies EIF4A3 as a novel oncogene in hepatocellular carcinoma acting through the modulation of FGFR4 splicing.Clinical and translational medicine · 2022Article
- A Potential miR-1246-5p-H3K27ac-NOL12 Regulatory Axis and Its Putative Tumour-Promoting Function in Hepatocellular Carcinoma.IET systems biologyArticle
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionAltered splicing landscape is an emerging cancer hallmark; however, the dysregulation and implication of the cellular machinery controlling this process (spliceosome components and splicing factors) in hepatocellular carcinoma (HCC) is poorly known. This study aimed to comprehensively characterize the spliceosomal profile and explore its role in HCC.
methodsExpression levels of 70 selected spliceosome components and splicing factors and clinical implications were evaluated in two retrospective and six in silico HCC cohorts. Functional, molecular and mechanistic studies were implemented in three cell lines (HepG2, Hep3B and SNU-387) and preclinical Hep3B-induced xenograft tumours.
resultsSpliceosomal dysregulations were consistently found in retrospective and in silico cohorts. EIF4A3, RBM3, ESRP2 and SRPK1 were the most dysregulated spliceosome elements in HCC. EIF4A3 expression was associated with decreased survival and greater recurrence. Plasma EIF4A3 levels were significantly elevated in HCC patients. In vitro EIF4A3-silencing (or pharmacological inhibition) resulted in reduced aggressiveness, and hindered xenograft-tumours growth in vivo, whereas EIF4A3 overexpression increased tumour aggressiveness. EIF4A3-silencing altered the expression and splicing of key HCC-related genes, specially FGFR4. EIF4A3-silencing blocked the cellular response to the natural ligand of FGFR4, FGF19. Functional consequences of EIF4A3-silencing were mediated by FGFR4 splicing as the restoration of non-spliced FGFR4 full-length version blunted these effects, and FGFR4 inhibition did not exert further effects in EIF4A3-silenced cells.
conclusionsSplicing machinery is strongly dysregulated in HCC, providing a source of new diagnostic, prognostic and therapeutic options in HCC. EIF4A3 is consistently elevated in HCC patients and associated with tumour aggressiveness and mortality, through the modulation of FGFR4 splicing.
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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.