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Promoter Methylation of Tumor Suppressors in Thyroid Carcinoma: A Systematic Review
Sara Sheikholeslami1, Marjan Zarif-Yeganeh1, Samaneh Farashi2,3
1Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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.
Insights
Promoter hypermethylation of tumor suppressor genes is implicated in thyroid cancer progression. Aberrant methylation of key genes like RASSF1A and PTEN offers potential diagnostic biomarkers and therapeutic targets for thyroid malignancies.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Tumor suppressor genes are crucial for regulating cell cycle, differentiation, and apoptosis.
- Aberrant DNA methylation of these genes is linked to thyroid cancer initiation and progression.
- This review focuses on the impact of promoter hypermethylation on key tumor suppressor genes in thyroid cancer.
Purpose of the Study:
- To review the known impact of promoter hypermethylation on tumor suppressor genes involved in thyroid cancer cell growth and apoptosis.
- To identify potential diagnostic biomarkers and therapeutic targets in thyroid malignancies.
Main Methods:
- Searched major databases for research articles up to June 2020.
- Identified tumor suppressor genes modulated by methylation in thyroid carcinoma.
- Reviewed 26 studies based on inclusion and exclusion criteria.
Main Results:
- Inactivation of RASSF1A, DAPK1, SLCFA8, and TSHR via hypermethylation may activate BRAF/MEK/ERK pathways.
- RARβ2 and RUNX3 inactivation can impair cell cycle suppression and apoptosis induction.
- TIMP3 and PTEN inactivation may promote angiogenesis and invasion by affecting PIP3 and VEGF pathways.
Conclusions:
- Methylation status of key genes can aid in early diagnosis and differentiation of thyroid malignancies.
- These findings support the potential for drug repurposing and developing novel treatments for thyroid cancer.
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