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

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Item Type:Article
Title:The miRNA-kallikrein axis of interaction: a new dimension in the pathogenesis of prostate cancer
Creators Name:White, N.M.A. and Youssef, Y.M. and Fendler, A. and Stephan, C. and Jung, K. and Yousef, G.M.
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.
Keywords:Cancer Pathogenesis, Kallikrein, KLK, miRNA, Personalized Medicine, Prostate, Prostate Cancer, Tumor Markers
Source:Biological Chemistry
Publisher:de Gruyter
Page Range:379-389
Date:May 2012
Official Publication:https://doi.org/10.1515/hsz-2011-0246
PubMed:View item in PubMed

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