ArticleScientific reports2024
Micropeptide AF127577.4-ORF hidden in a lncRNA diminishes glioblastoma cell proliferation via the modulation of ERK2/METTL3 interaction.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed.
- Long non-coding RNAs in glioblastoma: from molecular drivers to therapeutic targets.Frontiers in immunology · 2026Review
- Micropeptides in the oncological dark matter: decoding their roles in tumor progression and therapy resistance.Journal of translational 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
- Long Non-Coding RNAs in Malignant Human Brain Tumors: Driving Forces Behind Progression and Therapy.International journal of molecular sciences · 2025Review
- Noncoding RNA and Alcohol Use Disorder: A Scoping Review of Current Research and Knowledge Gaps.Alcohol research : current reviews · 2025Article
- CircRNA and lncRNA-encoded peptide in diseases, an update review.Molecular cancer · 2024Review
- Review
- Microproteins unveiling new dimensions in cancer.Functional & integrative genomics · 2024Review
- The indispensability of methyltransferase-like 3 in the immune system: from maintaining homeostasis to driving function.Frontiers in immunology · 2024Review
- Harnessing Noncanonical Proteins for Next-Generation Drug Discovery and Diagnosis.WIREs mechanisms of diseaseReview
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Micropeptides hidden in long non-coding RNAs (lncRNAs) have been uncovered to program various cell-biological changes associated with malignant transformation-glioblastoma (GBM) cascade. Here, we identified and characterized a novel hidden micropeptide implicated in GBM. We screened potential candidate lncRNAs by establishing a workflow involving ribosome-bound lncRNAs, publicly available MS/MS data, and prognosis-related lncRNAs. Micropeptide expression was detected by western blot (WB), immunofluorescence (IF), and immunohistochemistry (IHC). Cell proliferation rate was assessed by calcein/PI staining and EdU assay. Proteins interacted with the micropeptide were analyzed by proteomics after co-immunoprecipitation (Co-IP). We discovered that lncRNA AF127577.4 indeed encoded an endogenous micropeptide, named AF127577.4-ORF. AF127577.4-ORF was associated with GBM clinical grade. In vitro, AF127577.4-ORF could suppress GBM cell proliferation. Moreover, AF127577.4-ORF reduced m6A methylation level of GBM cells. Mechanistically, AF127577.4-ORF diminished ERK2 interaction with m6A reader methyltransferase like 3 (METTL3) and downregulated phosphorylated ERK (p-ERK) level. The ERK inhibitor reduced p-ERK level and downregulated METTL3 protein expression. AF127577.4-ORF weakened the stability of METTL3 protein by ERK. Also, AF127577.4-ORF suppressed GBM cell proliferation via METTL3. Our study identifies a novel micropeptide AF127577.4-ORF hidden in a lncRNA, with a potent anti-proliferating function in GBM by diminishing METTL3 protein stability by reducing the ERK2/METTL3 interaction. This micropeptide may be beneficial for development of therapeutic strategies against GBM.
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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 Socratic graph.