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Cancer Lett. 2017 Jan 28;385:150-159. doi: 10.1016/j.canlet.2016.10.028. Epub 2016 Oct 27.

Epigenetic disruption of miR-130a promotes prostate cancer by targeting SEC23B and DEPDC1.

Author information

1
Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal; Biomedical Sciences Graduate Program, Institute of Biomedical Sciences Abel Salazar - University of Porto (ICBAS-UP), Porto, Portugal.
2
Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal.
3
Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Norway.
4
Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal; School of Allied Health Sciences (ESTSP), Polytechnic of Porto, Portugal.
5
Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Norway.
6
Department of Epidemiology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal.
7
Department of Urology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal.
8
Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal; Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal; Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Porto, Portugal.
9
Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal; Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Porto, Portugal. Electronic address: carmenjeronimo@ipoporto.min-saude.pt.

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.

KEYWORDS:

DEPDC1; Prostate cancer; SEC23B; miR's epigenetic regulation; miR-130a; miRNA

PMID:
27984115
DOI:
10.1016/j.canlet.2016.10.028
[Indexed for MEDLINE]

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