The Epigenetic Integrator UHRF1: on the Road to Become a Universal Biomarker for Cancer

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Sep 9

PMID 28881702

Citations 64

Authors

Waseem Ashraf

Abdulkhaleg Ibrahim

Mahmoud Alhosin

Liliyana Zaayter

Khalid Ouararhni

Christophe Papin

Tanveer Ahmad

Ali Hamiche

Yves Mely

Christian Bronner

Marc Mousli

Affiliations

Soon will be listed here.

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.

Citing Articles

Epigenetic Disordering Drives Stemness, Senescence Escape and Tumor Heterogeneity.

Magnani E, Macchi F, Randic T, Chen C, Madakashira B, Ranjan S bioRxiv. 2025; .

PMID: 39763773 PMC: 11703240. DOI: 10.1101/2024.12.29.629346.

Comprehensive analysis of single-cell and bulk RNA sequencing reveals postoperative progression markers for non-muscle invasive bladder cancer and predicts responses to immunotherapy.

Xiao Z, Liu X, Wang Y, Jiang S, Feng Y Discov Oncol. 2024; 15(1):649.

PMID: 39532830 PMC: 11557814. DOI: 10.1007/s12672-024-01548-2.

Management of triple-negative breast cancer by natural compounds through different mechanistic pathways.

Kaleem M, Thool M, Dumore N, Abdulrahman A, Ahmad W, Almostadi A Front Genet. 2024; 15:1440430.

PMID: 39130753 PMC: 11310065. DOI: 10.3389/fgene.2024.1440430.

Identification of differentially expressed tumour-related genes regulated by UHRF1-driven DNA methylation.

Dong Q, Gong C, Jiang Q, Liu Y, Hu Y, Wang D Sci Rep. 2024; 14(1):18371.

PMID: 39112494 PMC: 11306747. DOI: 10.1038/s41598-024-69110-2.

Loss of PPARα function promotes epigenetic dysregulation of lipid homeostasis driving ferroptosis and pyroptosis lipotoxicity in metabolic dysfunction associated Steatotic liver disease (MASLD).

Theys C, Vanderhaeghen T, Van Dijck E, Peleman C, Scheepers A, Ibrahim J Front Mol Med. 2024; 3:1283170.

PMID: 39086681 PMC: 11285560. DOI: 10.3389/fmmed.2023.1283170.

References

Lorenzato M, Caudroy S, Bronner C, Evrard G, Simon M, Durlach A . Cell cycle and/or proliferation markers: what is the best method to discriminate cervical high-grade lesions?. Hum Pathol. 2005; 36(10):1101-7. DOI: 10.1016/j.humpath.2005.07.016. View

Chen X, Cheung S, So S, Fan S, Barry C, Higgins J . Gene expression patterns in human liver cancers. Mol Biol Cell. 2002; 13(6):1929-39. PMC: 117615. DOI: 10.1091/mbc.02-02-0023. View

Zhang H, Liu H, Chen Y, Yang X, Wang P, Liu T . A cell cycle-dependent BRCA1-UHRF1 cascade regulates DNA double-strand break repair pathway choice. Nat Commun. 2016; 7:10201. PMC: 4728409. DOI: 10.1038/ncomms10201. View

Wang B, Lin G, Wang B, Yan M, He B, Zhang W . UHRF1 suppression promotes cell differentiation and reduces inflammatory reaction in anaplastic thyroid cancer. Oncotarget. 2018; 9(62):31945-31957. PMC: 6112835. DOI: 10.18632/oncotarget.10674. View

Bonapace I, Latella L, Papait R, Nicassio F, Sacco A, Muto M . Np95 is regulated by E1A during mitotic reactivation of terminally differentiated cells and is essential for S phase entry. J Cell Biol. 2002; 157(6):909-14. PMC: 2174046. DOI: 10.1083/jcb.200201025. View

Dai C, Shi D, Gu W . Negative regulation of the acetyltransferase TIP60-p53 interplay by UHRF1 (ubiquitin-like with PHD and RING finger domains 1). J Biol Chem. 2013; 288(27):19581-92. PMC: 3707659. DOI: 10.1074/jbc.M113.476606. View

Macaluso M, Montanari M, Noto P, Gregorio V, Bronner C, Giordano A . Epigenetic modulation of estrogen receptor-alpha by pRb family proteins: a novel mechanism in breast cancer. Cancer Res. 2007; 67(16):7731-7. DOI: 10.1158/0008-5472.CAN-07-1476. View

Alhosin M, Sharif T, Mousli M, Etienne-Selloum N, Fuhrmann G, Schini-Kerth V . Down-regulation of UHRF1, associated with re-expression of tumor suppressor genes, is a common feature of natural compounds exhibiting anti-cancer properties. J Exp Clin Cancer Res. 2011; 30:41. PMC: 3096999. DOI: 10.1186/1756-9966-30-41. View

Frauer C, Hoffmann T, Bultmann S, Casa V, Cardoso M, Antes I . Recognition of 5-hydroxymethylcytosine by the Uhrf1 SRA domain. PLoS One. 2011; 6(6):e21306. PMC: 3120858. DOI: 10.1371/journal.pone.0021306. View

10.

Li X, Xu J, Nie J, Fan S . Exogenous expression of UHRF1 promotes proliferation and metastasis of breast cancer cells. Oncol Rep. 2012; 28(1):375-83. DOI: 10.3892/or.2012.1792. View

11.

Arita K, Ariyoshi M, Tochio H, Nakamura Y, Shirakawa M . Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism. Nature. 2008; 455(7214):818-21. DOI: 10.1038/nature07249. View

12.

Unoki M, Nishidate T, Nakamura Y . ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain. Oncogene. 2004; 23(46):7601-10. DOI: 10.1038/sj.onc.1208053. View

13.

Hashimoto H, Horton J, Zhang X, Cheng X . UHRF1, a modular multi-domain protein, regulates replication-coupled crosstalk between DNA methylation and histone modifications. Epigenetics. 2008; 4(1):8-14. PMC: 2661099. DOI: 10.4161/epi.4.1.7370. View

14.

Sandoval J, Peiro-Chova L, Pallardo F, Garcia-Gimenez J . Epigenetic biomarkers in laboratory diagnostics: emerging approaches and opportunities. Expert Rev Mol Diagn. 2013; 13(5):457-71. DOI: 10.1586/erm.13.37. View

15.

Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A, Endo T . The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature. 2007; 450(7171):908-12. DOI: 10.1038/nature06397. View

16.

Dawson M, Kouzarides T . Cancer epigenetics: from mechanism to therapy. Cell. 2012; 150(1):12-27. DOI: 10.1016/j.cell.2012.06.013. View

17.

Jeltsch A, Jurkowska R . New concepts in DNA methylation. Trends Biochem Sci. 2014; 39(7):310-8. DOI: 10.1016/j.tibs.2014.05.002. View

18.

Ying L, Lin J, Qiu F, Cao M, Chen H, Liu Z . Epigenetic repression of regulator of G-protein signaling 2 by ubiquitin-like with PHD and ring-finger domain 1 promotes bladder cancer progression. FEBS J. 2014; 282(1):174-82. DOI: 10.1111/febs.13116. View

19.

Wang F, Yang Y, Shi C, Zhang P, Moyer M, Zhang H . UHRF1 promotes cell growth and metastasis through repression of p16(ink⁴a) in colorectal cancer. Ann Surg Oncol. 2012; 19(8):2753-62. DOI: 10.1245/s10434-011-2194-1. View

20.

Li X, Meng Q, Fan S . Adenovirus-mediated expression of UHRF1 reduces the radiosensitivity of cervical cancer HeLa cells to gamma-irradiation. Acta Pharmacol Sin. 2009; 30(4):458-66. PMC: 4002271. DOI: 10.1038/aps.2009.18. View