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Micropeptide AF127577.4-ORF hidden in a lncRNA diminishes glioblastoma cell proliferation via the modulation of ERK2/METTL3 interaction.

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  • معلومة اضافية
    • المصدر:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • الموضوع:
      RNA, Long Noncoding*/genetics ; RNA, Long Noncoding*/metabolism ; Glioblastoma*/genetics ; Glioblastoma*/metabolism ; Glioblastoma*/pathology ; Cell Proliferation* ; Mitogen-Activated Protein Kinase 1*/metabolism ; Mitogen-Activated Protein Kinase 1*/genetics ; Methyltransferases*/metabolism ; Methyltransferases*/genetics; Humans ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Brain Neoplasms/genetics ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Peptides/metabolism
    • نبذة مختصرة :
      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.
      (© 2024. The Author(s).)
    • References:
      Nat Med. 2011 Aug 07;17(9):1101-8. (PMID: 21822286)
      Nat Genet. 2018 Jun;50(6):783-789. (PMID: 29785014)
      J Ethnopharmacol. 2020 Oct 28;261:113071. (PMID: 32603676)
      Mol Cell. 2023 Feb 2;83(3):428-441. (PMID: 36736310)
      J Exp Clin Cancer Res. 2022 Apr 15;41(1):142. (PMID: 35428347)
      Mol Cell. 2020 Nov 19;80(4):633-647.e7. (PMID: 33217317)
      Cancer Immunol Res. 2021 Dec;9(12):1383-1399. (PMID: 34667108)
      Mol Cancer. 2020 Feb 4;19(1):22. (PMID: 32019587)
      Genome Biol. 2021 Jan 28;22(1):51. (PMID: 33509238)
      Semin Cancer Biol. 2019 Aug;57:45-51. (PMID: 30205139)
      Nat Commun. 2018 Oct 26;9(1):4475. (PMID: 30367041)
      Biomolecules. 2020 Apr 08;10(4):. (PMID: 32276417)
      Elife. 2016 Mar 07;5:e13722. (PMID: 26949251)
      Nucleic Acids Res. 2013 Jan;41(Database issue):D1063-9. (PMID: 23203882)
      Front Immunol. 2021 Nov 25;12:706936. (PMID: 34899682)
      Adv Drug Deliv Rev. 2021 Apr;171:108-138. (PMID: 33486006)
      Oncogene. 2018 Jan 25;37(4):522-533. (PMID: 28991227)
      Cell Death Dis. 2020 Jan 6;11(1):16. (PMID: 31907362)
      Genome Biol. 2003;4(5):P3. (PMID: 12734009)
      Nat Commun. 2021 Jan 8;12(1):177. (PMID: 33420027)
      Cell Res. 2017 May;27(5):604-605. (PMID: 28290465)
      J Cell Biochem. 2015 Mar;116(3):351-63. (PMID: 25290986)
      Cancer Lett. 2021 Jan 28;497:89-99. (PMID: 33038492)
      EMBO J. 2020 Jan 2;39(1):e102190. (PMID: 31755573)
      Aging (Albany NY). 2021 Oct 5;13(19):23108-23118. (PMID: 34611079)
      Radiat Oncol. 2021 Feb 18;16(1):36. (PMID: 33602305)
      Drug Discov Today. 2021 Nov;26(11):2559-2574. (PMID: 34126238)
      J Exp Clin Cancer Res. 2023 Jan 7;42(1):10. (PMID: 36609396)
      Cell Struct Funct. 2018 May 18;43(1):75-83. (PMID: 29643274)
      Commun Biol. 2022 Sep 5;5(1):908. (PMID: 36064747)
      Front Oncol. 2021 Jan 14;10:622294. (PMID: 33520729)
      PLoS One. 2011;6(9):e24657. (PMID: 21949741)
      Mol Ther. 2019 Oct 2;27(10):1718-1725. (PMID: 31526596)
    • Grant Information:
      LHGJ20210910 Henan Province medical science and technology research plan joint construction project; XYBSKYZZ201632 the Doctoral Scientific Research Foundation of Xinxiang Medical University; 2020GGJS150 Young Key Teachers in Colleges and Universities in Henan Province
    • Contributed Indexing:
      Keywords: ERK2; Glioblastoma; METTL3; Micropeptide; lncRNA AF127577.4
    • الرقم المعرف:
      0 (RNA, Long Noncoding)
      EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
      EC 2.1.1.62 (METTL3 protein, human)
      EC 2.7.11.24 (MAPK1 protein, human)
      EC 2.1.1.- (Methyltransferases)
      0 (Peptides)
    • الموضوع:
      Date Created: 20240527 Date Completed: 20240527 Latest Revision: 20240604
    • الموضوع:
      20240604
    • الرقم المعرف:
      PMC11130299
    • الرقم المعرف:
      10.1038/s41598-024-62710-y
    • الرقم المعرف:
      38802444