Miniatura

Fitxers

Oncotarget_2018_M Esteller.pdf (2.88 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2018-06-26

Llicència de publicació

cc by (c) Ferreira et al., 2018
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/125003

Circular RNA CpG island hypermethylation-associated silencing in human cancer

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.18632/oncotarget.25673

Resum

Noncoding RNAs (ncRNAs), such as microRNAs and long noncoding RNAs (lncRNAs), participate in cellular transformation. Work done in the last decade has also demonstrated that ncRNAs with growth-inhibitory functions can undergo promoter CpG island hypermethylation-associated silencing in tumorigenesis. Herein, we wondered whether circular RNAs (circRNAs), a type of RNA transcripts lacking 5′-3′ ends and forming closed loops that are gaining relevance in cancer biology, are also a target of epigenetic inactivation in tumors. To tackle this issue, we have used cancer cells genetically deficient for the DNA methyltransferase enzymes in conjuction with circRNA expression microarrays. We have found that the loss of DNA methylation provokes a release of circRNA silencing. In particular, we have identified that promoter CpG island hypermethylation of the genes TUSC3 (tumor suppressor candidate 3), POMT1 (protein O-mannosyltransferase 1), ATRNL1 (attractin-like 1) and SAMD4A (sterile alpha motif domain containing 4A) is linked to the transcriptional downregulation of both linear mRNA and the hosted circRNA. Although some circRNAs regulate the linear transcript, we did not observe changes in TUSC3 mRNA levels upon TUSC3 circ104557 overexpression. Interestingly, we found circRNA-mediated regulation of target miRNAs and an in vivo growth inhibitory effect upon TUSC3 circ104557 transduction. Data mining for 5′-end CpG island methylation of TUSC3, ATRNL1, POMT1 and SAMD4A in cancer cell lines and primary tumors showed that the epigenetic defect was commonly observed among different tumor types in association with the diminished expression of the corresponding transcript. Our findings support a role for circRNA DNA methylation-associated loss in human cancer.

Matèries

RNA, Càncer

Matèries (anglès)

Cancer

Citació

Col·leccions

Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
<b>Publicacions de projectes de recerca finançats per la UE</b>

Citació

FERREIRA, Humberto j., DAVALOS, Veronica, CASTRO DE MOURA, Manuel, SOLER, Marta, PÉREZ SALVIA, Montserrat, BUENO COSTA, Alberto, SETIÉN, Fernando, MORAN, Sebastian, VILLANUEVA GARATACHEA, Alberto, ESTELLER, Manel. Circular RNA CpG island hypermethylation-associated silencing in human cancer. _Oncotarget_. 2018. Vol. 9, núm. 49, pàgs. 29208-29219. [consulta: 24 de gener de 2026]. ISSN: 1949-2553. [Disponible a: https://hdl.handle.net/2445/125003]

Exportar metadades

JSON - METS

Compartir registre