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.