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A multiplatform approach identifies miR-152-3p as a common epigenetically regul...

Ramalho-Carvalho, João; Gonçalves, Celine Saraiva; Graça, Inês; Bidarra, David; Pereira-Silva, Eva; Salta, Sofia; Godinho, Maria Inês; Gomez, Antonio

Prostate cancer (PCa) is a major cause of morbidity and mortality in men worldwide. MicroRNAs are globally downregulated in PCa, especially in poorly differentiated tumors. Nonetheless, the underlying mechanisms are still elusive. Herein, using combined analysis of microRNAs expression and genomewide DNA methylation, we aimed to identify epigenetically downregulated microRNAs in PCa.


Downregulation of miR-130b~301b cluster is mediated by aberrant promoter methyl...

Ramalho-Carvalho, João; Pinho dos Santos Graça, Maria Inês; Gomez, Antonio; Oliveira, Jorge; Henrique, Rui; Esteller, Manel; Jerónimo, Carmen

Numerous DNA-damaging cellular stresses, including oncogene activation and DNA-damage response (DDR), may lead to cellular senescence. Previous observations linked microRNA deregulation with altered senescent patterns, prompting us to investigate whether epigenetic repression of microRNAs expression might disrupt senescence in prostate cancer (PCa) cells. Differential methylation mapping in prostate tissues was...


Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhan...

Léveillé, Nicolas; Melo, Carlos A.; Rooijers, Koos; Díaz-Lagares, Angel; Melo, Sonia A.; Korkmaz, Gozde; Lopes, Rui; Moqadam, Farhad Akbari; Maia, Ana R

p53 binds enhancers to regulate key target genes. Here, we globally mapped p53-regulated enhancers by looking at enhancer RNA (eRNA) production. Intriguingly, while many p53-induced enhancers contained p53-binding sites, most did not. As long non-coding RNAs (lncRNAs) are prominent regulators of chromatin dynamics, we hypothesized that p53-induced lncRNAs contribute to the activation of enhancers by p53. Among ...


Epigenetic disruption of the PIWI pathway in human spermatogenic disorders

Heyn, Holger; Ferreira, Humberto J.; Bassas, Lluís; Bonache, Sandra; Sayols, Sergi; Sandoval, Juan; Esteller, Manel; Larriba, Sara

Epigenetic changes are involved in a wide range of common human diseases. Although DNA methylation defects are known to be associated with male infertility in mice, their impact on human deficiency of sperm production has yet to be determined. We have assessed the global genomic DNA methylation profiles in human infertile male patients with spermatogenic disorders by using the Infinium Human Methylation27 BeadC...


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