ArticleMolecular cancer2022
A novel peptide encoded by N6-methyladenosine modified circMAP3K4 prevents apoptosis in hepatocellular carcinoma.
Article in Molecular cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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106 citing papers in PubMed, 135 citations in OpenAlex.
- The multifaceted role of 3-methyladenine in cancer therapy.Journal of physiology and biochemistry · 2026Review
- Noncoding RNA encoded peptides in tumors from discovery to mechanism and clinical translation.iScience · 2026Review
- The translational roles of circular RNAs in cancers and their underlying molecular mechanisms.Medical oncology (Northwood, London, England) · 2026Review
- Circular RNA as emerging precision therapeutics: from RNA regulation to peptide translation.Precision clinical medicine · 2026Review
- Decoding the functional network of circular RNAs encoding proteins in hepatocellular carcinoma: from carcinogenesis to clinical transformation.Journal of advanced research · 2026Review
- Peptides from the Shadows: Molecular Depth Insights and Clinical Horizons of Circular RNA-encoded Peptides in Gliomas.Neuromolecular medicine · 2026Review
- circFKBP8(5S,6)-encoded protein modulates α-synuclein expression in SH-SY5Y cells.Molecular biology reports · 2026Article
- Epitranscriptomic control of cancer hallmarks: Functions, mechanisms, and therapeutics of RNA modifications.Cancer cell · 2026Review
- Functional roles, mechanistic insights, and therapeutic potential of the IGF2BP family in viral infections and virus-associated cancers.Journal of molecular histology · 2026Review
- ALKBH5 deficiency suppresses hepatocarcinogenesis in mice via mActa pharmacologica Sinica · 2026Article
- Review
- CircAFF3 modulation of p53-ID2 signaling in the retinal pigment epithelium links inflammation with cell death in dry age-related macular degeneration.Frontiers in cell and developmental biology · 2026Article
- Expression Profiles, Biological Functions and Clinical Significance of Circular RNAs in Inflammatory Bowel Disease.Journal of inflammation research · 2026Review
- Unveiling the Role of circRNAs in Pyroptotic Signalling: From Molecular Crosstalk to Disease Modulation.Journal of cellular and molecular medicine · 2025Review
- Recent advances of circular RNAs in gastrointestinal cancer.World journal of clinical oncology · 2025Review
- Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review).International journal of oncology · 2025Review
- m6A modification of non‑coding RNA: Mechanisms, functions and potential values in human diseases (Review).International journal of molecular medicine · 2025Review
- METTL3 facilitates the translation of CircSIK2 during chicken myogenesis in an m6A dependent manner.PLoS genetics · 2025Article
- Conserved and distinct expression of circular RNAs in commercially used Marek's disease vaccine viruses.The Journal of general virology · 2025Article
- The biological roles and molecular mechanisms of m6A reader IGF2BP1 in the hallmarks of cancer.Genes & diseases · 2025Review
46 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCircular RNAs (circRNAs) regulate various biological activities and have been shown to play crucial roles in hepatocellular carcinoma (HCC) progression. However, only a few coding circRNAs have been identified in cancers, and their roles in HCC remain elusive. This study aimed to identify coding circRNAs and explore their function in HCC.
methodsCircMAP3K4 was selected from the CIRCpedia database. We performed a series of experiments to determine the characteristics and coding capacity of circMAP3K4. We then used in vivo and in vitro assays to investigate the biological function and mechanism of circMAP3K4 and its protein product, circMAP3K4-455aa, in HCC.
resultsWe found circMAP3K4 to be an upregulated circRNA with coding potential in HCC. IGF2BP1 recognized the circMAP3K4 N6-methyladenosine modification and promoted its translation into circMAP3K4-455aa. Functionally, circMAP3K4-455aa prevented cisplatin-induced apoptosis in HCC cells by interacting with AIF, thus protecting AIF from cleavage and decreasing its nuclear distribution. Moreover, circMAP3K4-455aa was degraded through the ubiquitin-proteasome E3 ligase MIB1 pathway. Clinically, a high level of circMAP3K4 is an independent prognostic factor for adverse overall survival and adverse disease-free survival of HCC patients.
conclusionsCircMAP3K4 is a highly expressed circRNA in HCC. Driven by m6A modification, circMAP3K4 encoded circMAP3K4-455aa, protected HCC cells from cisplatin exposure, and predicted worse prognosis of HCC patients. Targeting circMAP3K4-455aa may provide a new therapeutic strategy for HCC patients, especially for those with chemoresistance. CircMAP3K4 is a highly expressed circRNA in HCC. Driven by m6A modification, IGF2BP1 facilitates circMAP3K4 peptide translation, then the circMAP3K4 peptide inhibits AIF cleavage and nuclear distribution, preventing HCC cells from cell death under stress and promoting HCC progression.
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