Articles producció científica> Medicina i Cirurgia

Mitochondrial RNA methyltransferase TRMT61B is a new, potential biomarker and therapeutic target for highly aneuploid cancers

  • Identification data

    Identifier: imarina:9280213
    Authors:
    Martín AEpifano CVilaplana-Marti BHernández IMacías RIRMartínez-Ramírez ÁCerezo ACabezas-Sainz PGarranzo-Asensio MAmarilla-Quintana SGómez-Domínguez DCaleiras ECamps JGómez-López GGómez de Cedrón MRamírez de Molina ABarderas RSánchez LVelasco-Miguel SPérez de Castro I
    Abstract:
    Despite being frequently observed in cancer cells, chromosomal instability (CIN) and its immediate consequence, aneuploidy, trigger adverse effects on cellular homeostasis that need to be overcome by anti-stress mechanisms. As such, these safeguard responses represent a tumor-specific Achilles heel, since CIN and aneuploidy are rarely observed in normal cells. Recent data have revealed that epitranscriptomic marks catalyzed by RNA-modifying enzymes change under various stress insults. However, whether aneuploidy is associated with such RNA modifying pathways remains to be determined. Through an in silico search for aneuploidy biomarkers in cancer cells, we found TRMT61B, a mitochondrial RNA methyltransferase enzyme, to be associated with high levels of aneuploidy. Accordingly, TRMT61B protein levels are increased in tumor cell lines with an imbalanced karyotype as well as in different tumor types when compared to control tissues. Interestingly, while TRMT61B depletion induces senescence in melanoma cell lines with low levels of aneuploidy, it leads to apoptosis in cells with high levels. The therapeutic potential of these results was further validated by targeting TRMT61B in transwell and xenografts assays. We show that TRM61B depletion reduces the expression of several mitochondrial encoded proteins and limits mitochondrial function. Taken together, these results identify a new biomarker of aneuploidy in cancer cells that could potentially be used to selectively target highly aneuploid tumors.
  • Others:

    Author, as appears in the article.: Martín A; Epifano C; Vilaplana-Marti B; Hernández I; Macías RIR; Martínez-Ramírez Á; Cerezo A; Cabezas-Sainz P; Garranzo-Asensio M; Amarilla-Quintana S; Gómez-Domínguez D; Caleiras E; Camps J; Gómez-López G; Gómez de Cedrón M; Ramírez de Molina A; Barderas R; Sánchez L; Velasco-Miguel S; Pérez de Castro I
    Department: Medicina i Cirurgia
    URV's Author/s: Camps Andreu, Jorge
    Keywords: Translation Multidrug-resistance Methylome Metastasis Mechanisms Integration Gene-expression Chromosomal instability Autophagy Adaptation
    Abstract: Despite being frequently observed in cancer cells, chromosomal instability (CIN) and its immediate consequence, aneuploidy, trigger adverse effects on cellular homeostasis that need to be overcome by anti-stress mechanisms. As such, these safeguard responses represent a tumor-specific Achilles heel, since CIN and aneuploidy are rarely observed in normal cells. Recent data have revealed that epitranscriptomic marks catalyzed by RNA-modifying enzymes change under various stress insults. However, whether aneuploidy is associated with such RNA modifying pathways remains to be determined. Through an in silico search for aneuploidy biomarkers in cancer cells, we found TRMT61B, a mitochondrial RNA methyltransferase enzyme, to be associated with high levels of aneuploidy. Accordingly, TRMT61B protein levels are increased in tumor cell lines with an imbalanced karyotype as well as in different tumor types when compared to control tissues. Interestingly, while TRMT61B depletion induces senescence in melanoma cell lines with low levels of aneuploidy, it leads to apoptosis in cells with high levels. The therapeutic potential of these results was further validated by targeting TRMT61B in transwell and xenografts assays. We show that TRM61B depletion reduces the expression of several mitochondrial encoded proteins and limits mitochondrial function. Taken together, these results identify a new biomarker of aneuploidy in cancer cells that could potentially be used to selectively target highly aneuploid tumors.
    Thematic Areas: Molecular biology Medicina ii Medicina i Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Cell biology Biotecnología Biochemistry & molecular biology
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: jorge.camps@urv.cat
    Author identifier: 0000-0002-3165-3640
    Record's date: 2024-08-03
    Papper version: info:eu-repo/semantics/submittedVersion
    Link to the original source: https://www.nature.com/articles/s41418-022-01044-6
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Cell Death And Differentiation.
    APA: Martín A; Epifano C; Vilaplana-Marti B; Hernández I; Macías RIR; Martínez-Ramírez Á; Cerezo A; Cabezas-Sainz P; Garranzo-Asensio M; Amarilla-Quintana (2023). Mitochondrial RNA methyltransferase TRMT61B is a new, potential biomarker and therapeutic target for highly aneuploid cancers. Cell Death And Differentiation, (), -. DOI: 10.1038/s41418-022-01044-6
    Article's DOI: 10.1038/s41418-022-01044-6
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2023
    Publication Type: Journal Publications
  • Keywords:

    Biochemistry & Molecular Biology,Cell Biology,Molecular Biology
    Translation
    Multidrug-resistance
    Methylome
    Metastasis
    Mechanisms
    Integration
    Gene-expression
    Chromosomal instability
    Autophagy
    Adaptation
    Molecular biology
    Medicina ii
    Medicina i
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Cell biology
    Biotecnología
    Biochemistry & molecular biology
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