The miRNA-kallikrein axis of interaction: a new dimension in the pathogenesis of prostate cancer.

Abstract:

:Kallikrein-related peptidases (KLKs) are a family of serine proteases that were shown to be useful cancer biomarkers. KLKs have been shown to be dysregulated in prostate cancer (PCa). microRNAs (miRNAs) are short RNA nucleotides that negatively regulate gene expression and have been reportedly dysregulated in PCa. We compiled a comprehensive list of 55 miRNAs that are differentially expressed in PCa from previous microarray analysis and published literature. Target prediction analyses showed that 29 of these miRNAs are predicted to target 10 KLKs. Eight of these miRNAs were predicted to target more than one KLK. Quantitative real-time (qRT)-PCR demonstrated that there was an inverse correlation pattern in the expression (normal vs. cancer) between dysregulated miRNAs and their target KLKs. In addition, we experientially validated the miRNA-KLK interaction by transfecting miR-331-3p and miR-143 into a PCa cell line. Decreased expression of targets KLK4 and KLK10, respectively, and decreased cellular growth were observed. In addition to KLKs, dysregulated miRNAs were predicted to target other genes involved in the pathogenesis of PCa. These data show that miRNAs can contribute to KLK regulation in PCa. The miRNA-KLK axis of interaction projects a new element in the pathogenesis of PCa that may have therapeutic implications.

journal_name

Biol Chem

journal_title

Biological chemistry

authors

White NM,Youssef YM,Fendler A,Stephan C,Jung K,Yousef GM

doi

10.1515/hsz-2011-0246

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

379-89

issue

5

eissn

1431-6730

issn

1437-4315

pii

/j/bchm.2012.393.issue-5/hsz-2011-0246/hsz-2011-02

journal_volume

393

pub_type

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