Articles producció científica> Ciències Mèdiques Bàsiques

A novel cancer-germline transcript carrying pro-metastatic miR-105 and TET-targeting miR-767 induced by DNA hypomethylation in tumors

  • Dades identificatives

    Identificador: imarina:6387895
    Autors:
    Loriot AVan tongelen ABlanco JKlaessens SCannuyer Jvan Baren NDecottignies ADe Smet C
    Resum:
    Genome hypomethylation is a common epigenetic alteration in human tumors, where it often leads to aberrant activation of a group of germline-specific genes, commonly referred to as cancer-germline genes. The cellular functions and tumor promoting potential of these genes remain, however, largely uncertain. Here, we report identification of a novel cancer-germline transcript (CT-GABRA3) displaying DNA hypomethylation-dependent activation in various tumors, including melanoma and lung carcinoma. Importantly, CT-GABRA3 harbors a microRNA (miR-105), which has recently been identified as a promoter of cancer metastasis by its ability to weaken vascular endothelial barriers following exosomal secretion. CT-GABRA3 also carries a microRNA (miR-767) with predicted target sites in TET1 and TET3, two members of the fen-eleven-franslocation family of tumor suppressor genes, which are involved in the conversion of 5-methylcytosines to 5-hydroxymethylcytosines (5hmC) in DNA. Decreased TET activity is a hallmark of cancer; here, we provide evidence that aberrant activation of miR-767 contributes to this phenomenon. We demonstrate that miR-767 represses TET1/3 mRNA and protein expression and regulates genomic 5hmC levels. Additionally, we show that high CT-GABRA3 transcription correlates with reduced TET1 mRNA levels in vivo in lung tumors. Together, our study identified a cancer-germline gene that produces microRNAs with oncogenic potential. Moreover, our data indicate that DNA hypomethylation in tumors can contribute to reduced 5hmC levels via activation of a TET-targeting microRNA. © 2014 Landes Bioscience.
  • Altres:

    Autor segons l'article: Loriot A; Van tongelen A; Blanco J; Klaessens S; Cannuyer J; van Baren N; Decottignies A; De Smet C
    Departament: Ciències Mèdiques Bàsiques
    Autor/s de la URV: Blanco Pérez, Jordi
    Paraules clau: Tet genes Micrornas Dna methylation Cancer-germline or cancer-testis genes Cancer epigenetics tet genes dna methylation cancer-germline or cancer-testis genes cancer epigenetics
    Resum: Genome hypomethylation is a common epigenetic alteration in human tumors, where it often leads to aberrant activation of a group of germline-specific genes, commonly referred to as cancer-germline genes. The cellular functions and tumor promoting potential of these genes remain, however, largely uncertain. Here, we report identification of a novel cancer-germline transcript (CT-GABRA3) displaying DNA hypomethylation-dependent activation in various tumors, including melanoma and lung carcinoma. Importantly, CT-GABRA3 harbors a microRNA (miR-105), which has recently been identified as a promoter of cancer metastasis by its ability to weaken vascular endothelial barriers following exosomal secretion. CT-GABRA3 also carries a microRNA (miR-767) with predicted target sites in TET1 and TET3, two members of the fen-eleven-franslocation family of tumor suppressor genes, which are involved in the conversion of 5-methylcytosines to 5-hydroxymethylcytosines (5hmC) in DNA. Decreased TET activity is a hallmark of cancer; here, we provide evidence that aberrant activation of miR-767 contributes to this phenomenon. We demonstrate that miR-767 represses TET1/3 mRNA and protein expression and regulates genomic 5hmC levels. Additionally, we show that high CT-GABRA3 transcription correlates with reduced TET1 mRNA levels in vivo in lung tumors. Together, our study identified a cancer-germline gene that produces microRNAs with oncogenic potential. Moreover, our data indicate that DNA hypomethylation in tumors can contribute to reduced 5hmC levels via activation of a TET-targeting microRNA. © 2014 Landes Bioscience.
    Àrees temàtiques: Saúde coletiva Nutrição Molecular biology Medicine (miscellaneous) Medicina veterinaria Medicina iii Medicina i Genetics & heredity Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Cancer research Biotecnología Biochemistry & molecular biology
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 15592294
    Adreça de correu electrònic de l'autor: jordi.blanco@urv.cat
    Identificador de l'autor: 0000-0001-8016-0984
    Data d'alta del registre: 2024-09-07
    Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
    Enllaç font original: https://www.tandfonline.com/doi/full/10.4161/epi.29628
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Epigenetics. 9 (8): 1163-1171
    Referència de l'ítem segons les normes APA: Loriot A; Van tongelen A; Blanco J; Klaessens S; Cannuyer J; van Baren N; Decottignies A; De Smet C (2014). A novel cancer-germline transcript carrying pro-metastatic miR-105 and TET-targeting miR-767 induced by DNA hypomethylation in tumors. Epigenetics, 9(8), 1163-1171. DOI: 10.4161/epi.29628
    DOI de l'article: 10.4161/epi.29628
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2014
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Biochemistry & Molecular Biology,Cancer Research,Genetics & Heredity,Medicine (Miscellaneous),Molecular Biology
    Tet genes
    Micrornas
    Dna methylation
    Cancer-germline or cancer-testis genes
    Cancer epigenetics
    tet genes
    dna methylation
    cancer-germline or cancer-testis genes
    cancer epigenetics
    Saúde coletiva
    Nutrição
    Molecular biology
    Medicine (miscellaneous)
    Medicina veterinaria
    Medicina iii
    Medicina i
    Genetics & heredity
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Cancer research
    Biotecnología
    Biochemistry & molecular biology
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