Hypermethylation of miR-130b-301b affects senescence in prostatic cancer

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Hypermethylation of miR-130b-301b affects senescence in prostatic cancer

Friday, 17.03.2017


João Ramalho-Carvalho1,2,3, Inês Graça1,4, Antonio Gomez2,#, Jorge Oliveira5, Rui Henrique2,6,7, Manel Esteller2,8,9,*, and Carmen Jerónimo1,7,*, ‡

1Cancer Biology & Epigenetics Group – Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal;

2Cancer Epigenetics and Biology Program; Bellvitge Biomedical Research Institute; Barcelona, Catalonia, Spain;

3Biomedical Sciences Graduate Program, Institute of Biomedical Sciences Abel Salazar– University of Porto (ICBAS-UP), Porto, Portugal;

4School of Allied Health Sciences (ESTSP), Polytechnic of Porto, Porto, Portugal; 

5Department of Urology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal;

6Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal;

7Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar– University of Porto (ICBAS-UP), Porto, Portugal

8Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain;

9Department of Physiological Sciences II, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain;

Contributed equally


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 carried using Infinium HumanMethylation450 BeadChip. After validation of methylation and expression analyses in a larger series of prostate tissues, the functional role of the cluster miR-130b~301b was explored using in vitro studies testing cell viability, apoptosis, invasion and DNA damage in prostate cancer cell lines. Western blot and RT-qPCR were performed to support those observations. We found that the miR-130b~301b cluster directs epigenetic activation of cell cycle inhibitors required for DDR activation, thus stimulating the senescence-associated secretory phenotype (SASP). Furthermore, overexpression of miR-130b~301b cluster markedly reduced the malignant phenotype of PCa cells. Altogether, these data demonstrate that miR-130b~301b cluster overexpression might effectively induce PCa cell growth arrest through epigenetic regulation of proliferation-blocking genes and activation of cellular senescence.

: Journal of Hematology & Oncology

http://jhoonline.biomedcentral.com/articles/10.1186/s13045-017-0415-1