ArticleHepatology (Baltimore, Md.)2019
Long-Read RNA Sequencing Identifies Alternative Splice Variants in Hepatocellular Carcinoma and Tumor-Specific Isoforms.
Article in Hepatology (Baltimore, Md.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 116 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
- Meta-analysis of transcriptomic variation in T-cell populations reveals both variable and consistent signatures of gene expression and splicing.RNA (New York, N.Y.) · 2020Pooled it
- Validation of next‑generation sequencing‑derived circulating mRNA variants as potential diagnostic tools in hepatocellular carcinoma and cholangiocarcinoma.Oncology reports · 2026Article
- The expression landscape and clinical significance of cancer-specific RNA transcripts across human cancers.Journal of translational medicine · 2026Article
- Chimeric antigen receptor T cell targeting CD44E variant in HCC holds therapeutic potential.Molecular therapy. Oncology · 2026Article
- Full-length transcriptome atlas of porcine skeletal muscle reveals isoform-resolved genetic regulatory mechanisms for muscle growth.BMC genomics · 2026Article
- Inhibition of the U12-type splicing factor ZCRB1 mediates retention of the USP21 minor intron to suppress malignant progression in hepatocellular carcinoma.Hepatology international · 2026Article
- Vitamin D Receptor in Cancer: Biological Functions, Mechanistic Insights, and Clinical Relevance.Cancer management and research · 2026Review
- Long-Read Sequencing Reveals RNA Splicing Complexity in Human Diseases.Computational and structural biotechnology journal · 2026Review
- Beyond counting: how single-cell long-read sequencing turns transcriptome complexity into precision targets.Frontiers in oncology · 2026Review
- Genome-wide CRISPR screen identifies splicing factor SF3B4 in driving hepatocellular carcinoma.Science advances · 2025Article
- Guanine Nucleotide Exchange Factors and Small GTPases: Their Regulation and Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- ASO Author Reflections: SCNM1 as a Novel Driver of Hepatocellular Carcinoma and a Potential Therapeutic Target.Annals of surgical oncology · 2025Article
- Review
- Long-read RNA sequencing: A transformative technology for exploring transcriptome complexity in human diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- PPM1G-mediated TBL1X mRNA splicing promotes cell migration in hepatocellular carcinoma.Cancer science · 2025Article
- Steering research on mRNA splicing in cancer towards clinical translation.Nature reviews. Cancer · 2024Review
- Caspases compromise SLU7 and UPF1 stability and NMD activity during hepatocarcinogenesis.JHEP reports : innovation in hepatology · 2024Article
- Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer.World journal of clinical oncology · 2024Review
- Comprehensive Atlas of Alternative Splicing Reveals NSRP1 Promoting Adipogenesis throughInternational journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Alternative splicing (AS) allows generation of cell type-specific mRNA transcripts and contributes to hallmarks of cancer. Genome-wide analysis for AS in human hepatocellular carcinoma (HCC), however, is limited. We sought to obtain a comprehensive AS landscape in HCC and define tumor-associated variants. Single-molecule real-time long-read RNA sequencing was performed on patient-derived HCC cells, and presence of splice junctions was defined by SpliceMap-LSC-IDP algorithm. We obtained an all-inclusive map of annotated AS variants and further discovered 362 alternative spliced variants that are not previously reported in any database (neither RefSeq nor GENCODE). They were mostly derived from intron retention and early termination codon with an in-frame open reading frame in 81.5%. We corroborated many of these predicted unannotated and annotated variants to be tumor specific in an independent cohort of primary HCC tumors and matching nontumoral liver. Using the combined Sanger sequencing and TaqMan junction assays, unique and common expressions of spliced variants including enzyme regulators (ARHGEF2, SERPINH1), chromatin modifiers (DEK, CDK9, RBBP7), RNA-binding proteins (SRSF3, RBM27, MATR3, YBX1), and receptors (ADRM1, CD44v8-10, vitamin D receptor, ROR1) were determined in HCC tumors. We further focused functional investigations on ARHGEF2 variants (v1 and v3) that arise from the common amplified site chr.1q22 of HCC. Their biological significance underscores two major cancer hallmarks, namely cancer stemness and epithelial-to-mesenchymal transition-mediated cell invasion and migration, although v3 is consistently more potent than v1. Conclusion: Alternative isoforms and tumor-specific isoforms that arise from aberrant splicing are common during the liver tumorigenesis. Our results highlight insights gained from the analysis of AS in 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.