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TITLE:
A novel cancer-germline transcript carrying pro-metastatic miR-105 and TET-targeting miR-767 induced by DNA hypomethylation in tumors - imarina:6387895

URV's Author/s:Blanco Pérez, Jordi
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
Author's mail:jordi.blanco@urv.cat
Author identifier:0000-0001-8016-0984
Journal publication year:2014
Publication Type:Journal Publications
ISSN:15592294
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
Papper original source:Epigenetics. 9 (8): 1163-1171
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.
Article's DOI:10.4161/epi.29628
Link to the original source:https://www.tandfonline.com/doi/full/10.4161/epi.29628
Papper version:info:eu-repo/semantics/publishedVersion
licence for use:https://creativecommons.org/licenses/by/3.0/es/
Department:Ciències Mèdiques Bàsiques
Licence document URL:https://repositori.urv.cat/ca/proteccio-de-dades/
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
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
Entity:Universitat Rovira i Virgili
Record's date:2024-09-07
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