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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2016

Open Access 01-12-2016 | Review

Signalling pathways in UHRF1-dependent regulation of tumor suppressor genes in cancer

Authors: Mahmoud Alhosin, Ziad Omran, Mazin A. Zamzami, Abdulrahman L. Al-Malki, Hani Choudhry, Marc Mousli, Christian Bronner

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2016

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Abstract

Epigenetic silencing of tumor suppressor genes (TSGs) through DNA methylation and histone changes is a main hallmark of cancer. Ubiquitin-like with PHD and RING Finger domains 1 (UHRF1) is a potent oncogene overexpressed in various solid and haematological tumors and its high expression levels are associated with decreased expression of several TSGs including p16 INK4A , BRCA1, PPARG and KiSS1. Using its several functional domains, UHRF1 creates a strong coordinated dialogue between DNA methylation and histone post-translation modification changes causing the epigenetic silencing of TSGs which allows cancer cells to escape apoptosis. To ensure the silencing of TSGs during cell division, UHRF1 recruits several enzymes including histone deacetylase 1 (HDAC1), DNA methyltransferase 1 (DNMT1) and histone lysine methyltransferases G9a and Suv39H1 to the right place at the right moment. Several in vitro and in vivo works have reported the direct implication of the epigenetic player UHRF1 in tumorigenesis through the repression of TSGs expression and suggested UHRF1 as a promising target for cancer treatment. This review describes the molecular mechanisms underlying UHRF1 regulation in cancer and discusses its importance as a therapeutic target to induce the reactivation of TSGs and subsequent apoptosis.
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Metadata
Title
Signalling pathways in UHRF1-dependent regulation of tumor suppressor genes in cancer
Authors
Mahmoud Alhosin
Ziad Omran
Mazin A. Zamzami
Abdulrahman L. Al-Malki
Hani Choudhry
Marc Mousli
Christian Bronner
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2016
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-016-0453-5

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