Author, as appears in the article.: Loriot A; Van tongelen A; Blanco J; Klaessens S; Cannuyer J; van Baren N; Decottignies A; De Smet C
Department: Ciències Mèdiques Bàsiques
URV's Author/s: Blanco Pérez, Jordi
Keywords: 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
Abstract: 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.
Thematic Areas: 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
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 15592294
Author's mail: jordi.blanco@urv.cat
Author identifier: 0000-0001-8016-0984
Record's date: 2024-09-07
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.tandfonline.com/doi/full/10.4161/epi.29628
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Epigenetics. 9 (8): 1163-1171
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
Article's DOI: 10.4161/epi.29628
Entity: Universitat Rovira i Virgili
Journal publication year: 2014
Publication Type: Journal Publications