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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Epigenetic regulation of kallikrein-related peptidases: there is a whole new world out there

Maria D. Pasic1 / Ekaterina Olkhov1, 2 / Bharati Bapat1, 2 / 1, 3

1Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King’s College Circle, Toronto M5S-1A8, Ontario, Canada

2Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 60 Murray Street, Toronto M5T-3L9, Ontario, Canada

3Department of Laboratory Medicine, and the Keenan Research Centre in the Li Ka Shing Knowledge Institute, St Michael’s Hospital, 30 Bond Street, Toronto M5B-1W8, Ontario, Canada

Corresponding author

Citation Information: . Volume 393, Issue 5, Pages 319–330, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/hsz-2011-0273, May 2012

Publication History

Received:
2011-11-21
Accepted:
2012-01-20

Abstract

The human kallikreins are a cluster of 15 kallikreins and kallikrein-related peptidases (KLKs). Evidence shows the involvement of KLKs in a wide range of pathophysiological processes, and underscores their potential contribution to cancer, skin and neurodegenerative disorders. The control of KLK expression is not fully elucidated. Understanding the mechanisms controlling KLK expression is an essential step towards exploring the pathogenesis of several diseases and the use of KLKs as disease biomarkers and/or therapeutic targets. Recently, epigenetic changes (including methylation, histone modification and microRNAs [miRNAs]) have drawn attention as a new dimension for controlling KLK expression. Reports showed the effect of methylation on the expression of KLK genes. This was also shown to have potential utility as a prognostic marker in cancer. miRNAs are small RNAs that control the expression of their targets at the post-transcriptional level. Target prediction showed that KLKs are potential targets of miRNAs that are dysregulated in tumors, including prostate, kidney and ovarian cancers, with downstream effect on tumor proliferation. Experimental validation remains an essential step to confirm the KLK-miRNA interaction. Epigenetic regulation of KLKs holds promise for an array of therapeutic applications in many diseases including cancer.

Keywords: cancer; epigenetic; histone; kallikrein; methylation; miRNA

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