Epigenetic disruption of miR-130a promotes prostate cancer by targeting SEC23B and DEPDC1. (28th January 2017)

• Record Type: Journal Article
• Authors: Ramalho-Carvalho, João; Martins, João Barbosa; Cekaite, Lina; Sveen, Anita; Torres-Ferreira, Jorge; Graça, Inês; Costa-Pinheiro, Pedro; Eilertsen, Ina Andrassy; Antunes, Luís; Oliveira, Jorge; Lothe, Ragnhild A.; Henrique, Rui; Jerónimo, Carmen
• Is Part Of: Cancer letters. Volume 385(2017)
• Page Start: 150
• Page End: 159
• Publication Date: 2017-01-28
• Subjects: miR's epigenetic regulation -- miR-130a -- miRNA -- Prostate cancer -- SEC23B -- DEPDC1; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2016.10.028
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: MicroRNAs (miRNAs) are small, non-coding RNAs that mediate post-transcriptional gene silencing, fine tuning gene expression. In an initial screen, miRNAs were found to be globally down-regulated in prostate cancer (PCa) cell lines and primary tumours. Exposure of PCa cell lines to a demethylating agent, 5-Aza-CdR resulted in an increase in the expression levels of miRNAs in general. Using stringent filtering criteria miR-130a was identified as the most promising candidate and selected for validation analyses in our patient series. Down-regulation of miR-130a was associated with promoter hypermethylation. MiR-130a methylation levels discriminated PCa from non-malignant tissues (AUC = 0.956), and urine samples revealed high specificity for non-invasive detection of patients with PCa (AUC = 0.89). Additionally, repressive histone marks were also found in the promoter of miR-130a. Over-expression of miR-130a in PCa cells reduced cell viability and invasion capability, and increased apoptosis. Putative targets of miR-130a were assessed by microarray expression profiling and DEPD1C and SEC23B were selected for validation. Silencing of both genes resembled the effect of over-expressing miR-130a in PCa cells. Our data indicate that miR-130a is an epigenetically regulated miRNA involved in regulation of key molecular and phenotypic features of prostate carcinogenesis, acting as a tumour suppressor miRNA. Highlights: The global microRNA downregulation observed in Prostate Cancer is a combined result of epigenetic and microRNA biogenesis machinery's alterations. miR-130a is a new epigenetically regulated, tumour-suppressor miRNA critical for reversion of Prostate cancer cells malignant phenotype. SEC23B and DEPDC1 are specific targets of miR-130a and contribute to the prostatic carcinogenesis. miR-130a is a specific prostate cancer biomarker.