2. Academic Validation
  3. Targeting microRNA/UHRF1 pathways as a novel strategy for cancer therapy

Targeting microRNA/UHRF1 pathways as a novel strategy for cancer therapy

  • Oncol Lett. 2018 Jan;15(1):3-10. doi: 10.3892/ol.2017.7290.
Hani Choudhry 1 2 3 4,  Mazin A Zamzami 1 2 3,  Ziad Omran 5,  Wei Wu 6,  Marc Mousli 7,  Christian Bronner 8,  Mahmoud Alhosin 1 2 3
Affiliations

Affiliations

  • 1 Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  • 2 Cancer Metabolism and Epigenetic Unit, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  • 3 Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  • 4 Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  • 5 College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
  • 6 Department of Medicine, University of California, San Francisco, CA 94143, USA.
  • 7 Laboratory of Biophotonics and Pharmacology, Faculty of Pharmacy, University of Strasbourg, 67401 Illkirch Cedex, France.
  • 8 Institute of Genetics and Molecular and Cellular Biology (IGBMC), National Institute of Health and Medical Research U964, National Center for Scientific Research UMR7104, University of Strasbourg, 67404 Illkirch Cedex, France.
PMID: 29285183 DOI: 10.3892/ol.2017.7290
Abstract

Ubiquitin-like containing plant homeodomain and RING finger domains 1 (UHRF1) is an anti-apoptotic protein involved in the silencing of several tumor suppressor genes (TSGs) through epigenetic modifications including DNA methylation and histone post-translational alterations, and also epigenetic-independent mechanisms. UHRF1 overexpression is observed in a number of solid tumors and hematological malignancies, and is considered a primary mechanism in inhibiting Apoptosis. UHRF1 exerts its inhibitory activity on TSGs by binding to functional domains and therefore influences several epigenetic actors including DNA Methyltransferase, histone deacetylase 1, Histone Acetyltransferase Tat-interacting protein 60 and histone methyltransferases G9a and Suv39H1. UHRF1 is considered to control a large macromolecular protein complex termed epigenetic code replication machinery, in order to maintain epigenetic silencing of TSGs during cell division, thus enabling Cancer cells to escape Apoptosis. MicroRNAs (miRNAs) are able to regulate the expression of its target gene by functioning as either an oncogene or a tumor suppressor. In the present review, the role of tumor suppressive miRNAs in the regulation of UHRF1, and the importance of targeting the MicroRNA/UHRF1 pathways in order to induce the reactivation of silenced TSGs and subsequent Apoptosis are discussed.

Keywords

DNA methylation; apoptosis; cancer; epigenetics; microRNA; tumor suppressor genes; ubiquitin-like with PHD and RING finger domains 1.

Figures