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Clinical Epigenetics

, 7:42

First Online: 10 April 2015Received: 01 December 2014Accepted: 19 March 2015


BackgroundProstate cancer PCa, a highly incident and heterogeneous malignancy, mostly affects men from developed countries. Increased knowledge of the biological mechanisms underlying PCa onset and progression are critical for improved clinical management. MicroRNAs miRNAs deregulation is common in human cancers, and understanding how it impacts in PCa is of major importance. MiRNAs are mostly downregulated in cancer, although some are overexpressed, playing a critical role in tumor initiation and progression. We aimed to identify miRNAs overexpressed in PCa and subsequently determine its impact in tumorigenesis.

ResultsMicroRNA expression profiling in primary PCa and morphological normal prostate MNPT tissues identified 17 miRNAs significantly overexpressed in PCa. Expression of three miRNAs, not previously associated with PCa, was subsequently assessed in large independent sets of primary tumors, in which miR-182 and miR-375 were validated, but not miR-32. Significantly higher expression levels of miR-375 were depicted in patients with higher Gleason score and more advanced pathological stage, as well as with regional lymph nodes metastases. Forced expression of miR-375 in PC-3 cells, which display the lowest miR-375 levels among PCa cell lines, increased apoptosis and reduced invasion ability and cell viability. Intriguingly, in 22Rv1 cells, which displayed the highest miR-375 expression, knockdown experiments also attenuated the malignant phenotype. Gene ontology analysis implicated miR-375 in several key pathways deregulated in PCa, including cell cycle and cell differentiation. Moreover, CCND2 was identified as putative miR-375 target in PCa, confirmed by luciferase assay.

ConclusionsA dual role for miR-375 in prostate cancer progression is suggested, highlighting the importance of cellular context on microRNA targeting.

KeywordsProstate cancer MicroRNAs Epigenetics miR-375 CCND2 João Ramalho-Carvalho, Filipa Quintela Vieira and Carmen Jerónimo contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s13148-015-0076-2 contains supplementary material, which is available to authorized users.

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Autor: Pedro Costa-Pinheiro - João Ramalho-Carvalho - Filipa Quintela Vieira - Jorge Torres-Ferreira - Jorge Oliveira - Céline S

Fuente: https://link.springer.com/

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