Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/125003
Title: | Circular RNA CpG island hypermethylation-associated silencing in human cancer |
Author: | 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 |
Keywords: | RNA Càncer Cancer |
Issue Date: | 26-Jun-2018 |
Publisher: | Impact Journals |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.25673 |
It is part of: | Oncotarget, 2018, vol. 9, num. 49, p. 29208-29219 |
URI: | http://hdl.handle.net/2445/125003 |
Related resource: | https://doi.org/10.18632/oncotarget.25673 |
ISSN: | 1949-2553 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Publicacions de projectes de recerca finançats per la UE |
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Oncotarget_2018_M Esteller.pdf | 2.95 MB | Adobe PDF | View/Open |
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