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Int. J. Mol. Sci. 2017, 18(7), 1361; doi:10.3390/ijms18071361

Epigenetic Regulation of the Biosynthesis & Enzymatic Modification of Heparan Sulfate Proteoglycans: Implications for Tumorigenesis and Cancer Biomarkers

1
Biomedical Sciences Program, College of Health Sciences, Midwestern University, Glendale, AZ 85308, USA
2
Department of Microbiology & Immunology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ 85308, USA
*
Author to whom correspondence should be addressed.
Received: 1 May 2017 / Revised: 5 June 2017 / Accepted: 22 June 2017 / Published: 26 June 2017
(This article belongs to the Special Issue Cancer Epigenetics)
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Abstract

Emerging evidence suggests that the enzymes in the biosynthetic pathway for the synthesis of heparan sulfate moieties of heparan sulfate proteoglycans (HSPGs) are epigenetically regulated at many levels. As the exact composition of the heparan sulfate portion of the resulting HSPG molecules is critical to the broad spectrum of biological processes involved in oncogenesis, the epigenetic regulation of heparan sulfate biosynthesis has far-reaching effects on many cellular activities related to cancer progression. Given the current focus on developing new anti-cancer therapeutics focused on epigenetic targets, it is important to understand the effects that these emerging therapeutics may have on the synthesis of HSPGs as alterations in HSPG composition may have profound and unanticipated effects. As an introduction, this review will briefly summarize the variety of important roles which HSPGs play in a wide-spectrum of cancer-related cellular and physiological functions and then describe the biosynthesis of the heparan sulfate chains of HSPGs, including how alterations observed in cancer cells serve as potential biomarkers. This review will then focus on detailing the multiple levels of epigenetic regulation of the enzymes in the heparan sulfate synthesis pathway with a particular focus on regulation by miRNA and effects of epigenetic therapies on HSPGs. We will also explore the use of lectins to detect differences in heparan sulfate composition and preview their potential diagnostic and prognostic use in the clinic. View Full-Text
Keywords: biomarkers; biosynthetic pathways; enzymatic modification; epigenetic regulation; glycosylation; heparan sulfate proteoglycans; lectin arrays; sulfation biomarkers; biosynthetic pathways; enzymatic modification; epigenetic regulation; glycosylation; heparan sulfate proteoglycans; lectin arrays; sulfation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Hull, E.E.; Montgomery, M.R.; Leyva, K.J. Epigenetic Regulation of the Biosynthesis & Enzymatic Modification of Heparan Sulfate Proteoglycans: Implications for Tumorigenesis and Cancer Biomarkers. Int. J. Mol. Sci. 2017, 18, 1361.

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