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Review
. 2017 Apr 24;8(31):51946-51962.
doi: 10.18632/oncotarget.17393. eCollection 2017 Aug 1.

The epigenetic integrator UHRF1: on the road to become a universal biomarker for cancer

Waseem Ashraf  1 , Abdulkhaleg Ibrahim  2 , Mahmoud Alhosin  3   4   5 , Liliyana Zaayter  1 , Khalid Ouararhni  2 , Christophe Papin  2 , Tanveer Ahmad  1 , Ali Hamiche  2 , Yves Mély  1 , Christian Bronner #  2 , Marc Mousli #  1
Affiliations
Review

The epigenetic integrator UHRF1: on the road to become a universal biomarker for cancer

Waseem Ashraf et al. Oncotarget. .

Abstract

Cancer is one of the deadliest diseases in the world causing record number of mortalities in both developed and undeveloped countries. Despite a lot of advances and breakthroughs in the field of oncology still, it is very hard to diagnose and treat the cancers at early stages. Here in this review we analyze the potential of Ubiquitin-like containing PHD and Ring Finger domain 1 (UHRF1) as a universal biomarker for cancers. UHRF1 is an important epigenetic regulator maintaining DNA methylation and histone code in the cell. It is highly expressed in a variety of cancers and is a well-known oncogene that can disrupt the epigenetic code and override the senescence machinery. Many studies have validated UHRF1 as a powerful diagnostic and prognostic tool to differentially diagnose cancer, predict the therapeutic response and assess the risk of tumor progression and recurrence. Highly sensitive, non-invasive and cost effective approaches are therefore needed to assess the level of UHRF1 in patients, which can be deployed in diagnostic laboratories to detect cancer and monitor disease progression.

Keywords: DNA methylation; UHRF1; biomarkers; cancer; epigenetics.

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Conflict of interest statement

CONFLICTS OF INTEREST All authors report no conflicts of interest.

Figures

Figure 1
Figure 1. Structure of UHRF1 protein
Structure of UHRF1 protein showing the different domains and their functions. The protein contains 793 amino acids and five major domains: UBL (ubiquitin-like) domain, TTD (Tandem Tudor Domain), PHD (Plant Homeodomain), SRA (Set and Ring Associated) domain and RING (Really Interesting New Gene) domain.
Figure 2
Figure 2. Regulation mechanisms of UHRF1
Different transcription factors like E2F1, E2F8, Sp1, FOXM1, NFκB (indicated in green) enhance while others such as YY1 along with lysine methyl transferase G9a (indicated in red) repress the expression of UHRF1 at transcription level. Many small non-coding microRNAs also decrease UHRF1 expression by destabilizing UHRF1 mRNA through binding to 3’UTR region. UHRF1 protein is degraded by proteosomal pathway after autoubiquitinylation or ubiquitinylation by SCFβ-TrCP E3 ligase. Ubiquitinylated UHRF1 is stabilized in cells by USP7, HSP90 or UPAT lnRNA. Increased transcription factor expression, downregulation of miRNAs and increased levels of stabilizing factors (all indicated in green) result in overexpression of UHRF1.
Figure 3
Figure 3. Overexpression of UHRF1 promotes tumorigenesis in different cancers
UHRF1 overexpression leads to epigenetic abnormalities including DNA methylation and downregulation of tumor suppressor genes or lnRNAs. Figure is made using images taken with permission from Servier Medical Arts http://servier.com/Powerpoint-image-bank.
See this image and copyright information in PMC

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