Promoter Methylation of Tumor Suppressors in Thyroid Carci-noma: A Systematic Review

Sara  Sheikholeslami; Marjan  Zarif -Yeganeh; Samaneh  Farashi; Fereidoun  Azizi; Sima  Kheradmand Kia; Ladan  Teimoori-Toolabi; Mehdi  Hedayati

doi:10.18502/ijph.v50i12.7928

Sara Sheikholeslami Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Marjan Zarif -Yeganeh Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Samaneh Farashi Cancer Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Australian Prostate Cancer Re-search Centre-Queensland, Queensland University of Technology, Brisbane, Queensland, 4102, Australia
Fereidoun Azizi Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Sima Kheradmand Kia Laboratory for Red Blood Cell Diagnostics, Sanquin, Amsterdam, Netherlands
Ladan Teimoori-Toolabi Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
Mehdi Hedayati Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijph.v50i12.7928

Keywords: DNA methylation; Tumor suppressor gene; Epigenetic; Thyroid cancer; Neoplasm

Abstract

Background: The tumor suppressor genes play a critical role in cellular and molecular mechanisms such as cell cycle processes, cell differentiation and apoptosis. Aberrant DNA methylation of tumor suppressor genes and subsequent gene expression changes have shown to be involved in the initiation and progression of various malignancies including thyroid malignancies. In this review, we investigated what is known about the impact of promoter hypermethylation on the key tumor suppressor genes known to be involved in cell growth and/or apoptosis of thyroid cancer.

Methods: The most important databases were searched for research articles until June 2020 to identify reported tumor suppressor genes that are modulated by methylation modulation changes in thyroid carcinoma. Following the inclusion and exclusion criteria, 26 studies were reviewed using the full text to meet the inclusion and exclusion criteria.

Results: The tumor suppressor genes reviewed here are suggestive biomarkers and potential targetable drugs. Inactivation of RASSF1A, DAPK1, SLCFA8, and TSHR through aberrant epigenetic methylation could activate BRAF/MEK/ERK kinase pathways with potential clinical implications in thyroid cancer patients. RARβ2 and RUNX3 could suppress cell cycle and induce apoptosis in malignant cells. TIMP3 and PTEN could prevent angiogenesis and invasion through PIP3 pathway and arrest VEFG activity.

Conclusion: The methylation status of key genes in various types of thyroid malignancies could be used in early diagnosis as well as differentiation of malignant and benign thyroid. This is valuable in drug repurposing and discovering alternative treatments or preventions in thyroid cancer.