The Epigenetic Modification of SLC5A8 in Papillary Thyroid Carcinoma and its Effects on Clinic-Pathological Features

Sara  Sheikholeslami; Fereidoun  Azizi; Asghar  Ghasemi; Abbas  Alibakhshi; Hossein Parsa; Setareh  Shivaee; Marjan  Zarif-Yeganeh; Mehdi  Hedayati; Ladan  Teimoori-Toolabi

doi:10.18502/ijph.v51i3.8940

Sara Sheikholeslami Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Fereidoun Azizi Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Asghar Ghasemi Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abbas Alibakhshi Department of General Surgery, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
Hossein Parsa Department of Surgery, Velayat Hospital, Qazvin University of Medical Sciences, Qazvin, Iran
Setareh Shivaee 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
Mehdi Hedayati Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Ladan Teimoori-Toolabi Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

DOI: https://doi.org/10.18502/ijph.v51i3.8940

Keywords: DNA methylation; Gene expression; Genes; Tumor suppressor; Thyroid cancer; Papillary

Abstract

Background: Epigenetic alterations such as DNA methylation are known as the main cause of different types of cancers through inactivation of tumor suppressor genes, especially thyroid cancer. Identification of novel and effective markers are important in diagnosis and prevention of thyroid cancer. In the present study, the expression and methylation of Solute carrier family 5 member 8 (SLC5A8) in Papillary Thyroid Carcinoma (PTC) in comparison to multinodular goiter (MNG) have been studied.

Methods: Overall, 41 patients with PTC and 36 patients affected by MNG were recruited from four hospitals in Tehran and Qazvin, Iran in 2018. Thyroid tissues were obtained during thyroidectomy. RNA and DNA were extracted from thyroid tissues. Quantitative RT-PCR assay was performed for determining the mRNA level of SLC5A8 while Methylation-Sensitive High-Resolution Methylation was applied for assessing the methylation status.

Results: Methylation status of three regions composed of 52 CpG islands in the promoter of SLC5A8 gene was studied by HRM assay. SLC5A8 level in PTC tissues was significantly downregulated in average 0.4 fold in comparison with MNG tissues (P=0.05). The aberrant methylation of SLC5A8 (b) region was remarkably different in PTC and MNG cases. The promoter methylation of SLC5A8 (c) was significantly related to BRAF mutations and vascular invasion in PTC patients.

Conclusion: The aberrant promoter hyper methylation of SLC5A8 was related to aggressive PTC. Therefore, there is some evidence to support the hypothesis that SLC5A8 could be a paly important role in the development of PTC.