ArticleOncogene2022
HNF4A-AS1-encoded small peptide promotes self-renewal and aggressiveness of neuroblastoma stem cells via eEF1A1-repressed SMAD4 transactivation.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Functions of exosome-derived noncoding RNA-encoded polypeptides/proteins in human diseases.Genes & diseases · 2027Review
- Pasta, a Versatile Transcriptomic Clock, Maps the Chemical and Genetic Determinants of Aging and Rejuvenation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nortriptyline Inhibits Lysosomal Exocytosis-Mediated SASP During Gastric Cancer Progression via Targeting HOXA1-PITX2 Phase Separation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Prognostic value of a lncRNA signature in early-stage invasive breast cancer patients.Cancer cell international · 2025Article
- Beyond the Transcript: Translating Non-Coding RNAs and Their Impact on Cellular Regulation.Cancers · 2025Review
- Peptidergic Systems and Neuroblastoma.International journal of molecular sciences · 2025Review
- Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance.Molecular cancer · 2025Review
- Noncoding RNA-encoded peptides in cancer: biological functions, posttranslational modifications and therapeutic potential.Journal of hematology & oncology · 2025Review
- Microproteins in cancer: identification, biological functions, and clinical implications.Trends in genetics : TIG · 2025Review
- CircRNA and lncRNA-encoded peptide in diseases, an update review.Molecular cancer · 2024Review
- Noncanonical microprotein regulation of immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- LncRNA-encoded peptides in cancer.Journal of hematology & oncology · 2024Review
- Beyond traditional translation: ncRNA derived peptides as modulators of tumor behaviors.Journal of biomedical science · 2024Review
- Targeting c-Myc transactivation by LMNA inhibits tRNA processing essential for malate-aspartate shuttle and tumour progression.Clinical and translational medicine · 2024Article
- HNF4A-AS1 inhibits the progression of hepatocellular carcinoma by promoting the ubiquitin-modulated degradation of PCBP2 and suppressing the stability of ARG2 mRNA.International journal of biological sciences · 2024Article
- High eEF1A1 Protein Levels Mark Aggressive Prostate Cancers and the In Vitro Targeting of eEF1A1 Reveals the eEF1A1-actin Complex as a New Potential Target for Therapy.International journal of molecular sciences · 2022Article
- Natural antisense transcripts as drug targets.Frontiers in molecular biosciences · 2022Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer stem cells play crucial roles in tumorigenesis and aggressiveness, while regulatory mechanisms in neuroblastoma (NB), a pediatric extracranial malignancy with highest incidence, are still unknown. Herein, a small 51-amino acid peptide (sPEP1) encoded by hepatocyte nuclear factor 4 alpha antisense RNA 1 (HNF4A-AS1) was identified in tumor tissues and cells, which facilitated self-renewal and aggressiveness of NB stem cells. MiRNA-409-5p interacted with HNF4A-AS1 to facilitate sPEP1 translation via recruiting eukaryotic translation initiation factor 3 subunit G, while sPEP1 repressed serum deprivation-induced senescence and promoted sphere formation, growth, or metastasis of NB stem cells. Mechanistically, sPEP1 directly interacted with eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) to facilitate its binding to SMAD family member 4 (SMAD4), resulting in repression of SMAD4 transactivation and transcriptional upregulation of stem cell genes associated with tumor progression. Rescue experiments revealed that sPEP1 exerted oncogenic roles via facilitating physical interaction between eEF1A1 and SMAD4. Notably, knockdown of sPEP1 significantly repressed the self-renewal and metastasis of NB stem cells in vivo. High sPEP1 or eEF1A1 levels in clinical NB tissues were linked to poor patients' survival. These findings suggest that HNF4A-AS1-encoded sPEP1 promotes self-renewal and aggressive features of NB stem cells by eEF1A1-repressed SMAD4 transactivation.
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