# name
Circular RNA CpG island hypermethylation-associated silencing in human cancer

# metadata.dc.description.abstract[].value
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.

# metadata.dc.source[].value
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

# metadata.dc.title[].value
Circular RNA CpG island hypermethylation-associated silencing in human cancer