ArticleCell death and differentiation2023
A novel tumor suppressor encoded by a 1p36.3 lncRNA functions as a phosphoinositide-binding protein repressing AKT phosphorylation/activation and promoting autophagy.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 13 citations in OpenAlex.
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- Loss of E3 Ubiquitin Ligase RINES via CpG Methylation Relieves Suppression of STAT3 and MYC, Facilitating Multiple Tumorigeneses.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- Micropeptide colorectal neoplasia differentially expressed (CRNDE) 84aa encoded by CRNDE elicits a T-cell immune response to breast cancer.Translational cancer research · 2026Article
- Integrative analysis of RNA-seq and Ribo-seq reveals that lncRNA regulates chicken myogenesis through encoding peptide.Journal of animal science and biotechnology · 2026Article
- Complex landscape of somatic copy number alterations in head and neck paragangliomas.Frontiers in endocrinology · 2026Article
- RSPO4 exerts tumor suppression through antagonizing canonical and non-canonical Wnt signaling.International journal of biological sciences · 2026Article
- Autophagy inhibition improves the efficacy of anlotinib and PD-1 inhibitors in the treatment of NSCLC.Journal for immunotherapy of cancer · 2025Article
- Chemically modified non-coding RNAs in cancer.Expert reviews in molecular medicine · 2025Review
- Beyond the Transcript: Translating Non-Coding RNAs and Their Impact on Cellular Regulation.Cancers · 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
- CircRNA and lncRNA-encoded peptide in diseases, an update review.Molecular cancer · 2024Review
- Autophagy-related lncRNAs and exosomal lncRNAs in colorectal cancer: focusing on lncRNA-targeted strategies.Cancer cell international · 2024Review
- Non-canonical translation in cancer: significance and therapeutic potential of non-canonical ORFs, mCell death discovery · 2024Review
- LncRNA-encoded peptides in cancer.Journal of hematology & oncology · 2024Review
- Review
- Clinical prospects and research strategies of long non-coding RNA encoding micropeptides.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peptides/small proteins, encoded by noncanonical open reading frames (ORF) of previously claimed non-coding RNAs, have recently been recognized possessing important biological functions, but largely uncharacterized. 1p36 is an important tumor suppressor gene (TSG) locus frequently deleted in multiple cancers, with critical TSGs like TP73, PRDM16, and CHD5 already validated. Our CpG methylome analysis identified a silenced 1p36.3 gene KIAA0495, previously thought coding long non-coding RNA. We found that the open reading frame 2 of KIAA0495 is actually protein-coding and translating, encoding a small protein SP0495. KIAA0495 transcript is broadly expressed in multiple normal tissues, but frequently silenced by promoter CpG methylation in multiple tumor cell lines and primary tumors including colorectal, esophageal and breast cancers. Its downregulation/methylation is associated with poor survival of cancer patients. SP0495 induces tumor cell apoptosis, cell cycle arrest, senescence and autophagy, and inhibits tumor cell growth in vitro and in vivo. Mechanistically, SP0495 binds to phosphoinositides (PtdIns(3)P, PtdIns(3,5)P2) as a lipid-binding protein, inhibits AKT phosphorylation and its downstream signaling, and further represses oncogenic AKT/mTOR, NF-κB, and Wnt/β-catenin signaling. SP0495 also regulates the stability of autophagy regulators BECN1 and SQSTM1/p62 through modulating phosphoinositides turnover and autophagic/proteasomal degradation. Thus, we discovered and validated a 1p36.3 small protein SP0495, functioning as a novel tumor suppressor regulating AKT signaling activation and autophagy as a phosphoinositide-binding protein, being frequently inactivated by promoter methylation in multiple tumors as a potential biomarker.
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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.