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Arch Iran Med. 2022;25(3): 171-177.
doi: 10.34172/aim.2022.29

Scopus ID: 85128487723
  Abstract View: 1774
  PDF Download: 1019

Original Article

CpG Island Methylation of the Rap1Gap Gene in Medullary Thyroid Cancer

Bita Faam 1 ORCID logo, Ata. A Ghadiri 1,2, Mohammad Ali Ghaffari 1, Mehdi Totonchi 3, Atieh Amouzegar 4, Fereidoun Azizi 4, Hajiehbibi Shahbazian 5, Mahmoud Hashemitabar 6, Seyed Ahmad Fanaei 7, Layasadat Khorsandi 1,6* ORCID logo

1 Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2 Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3 Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
4 Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5 Chronic Disease Care Research Center, School of Nursing and Midwifery, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
6 Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
7 Erfan Grand Hospital, Tehran, Iran
*Corresponding Author: *Corresponding Author: Layasadat Khorsandi, PhD; Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, P.O.Box: 61335, Iran. Tel:+98-613-3336380; Fax:+98-613-3336380; Email: , Email: khorsandi_cmrc@yahoo.com

Abstract

Background: Medullary thyroid cancer (MTC) is a rare type of neuroendocrine tumor. This study aimed to investigate the gene and protein expression of RAP1GAP and DNA methylation patterns of its CpG74a , CpG74b , and CpG24 in an Iranian population with MTC.

Methods: In this case-control study, we selected 55 individuals who underwent thyroidectomy in Erfan hospital, Tehran, between 2018 and 2020. Samples were divided into normal thyroid tissues (control; n=20), benign nodule (n=20), and MTC (n=15). DNA methylation patterns were investigated using MSP (methylation-specific PCR). The protein level and mRNA expression of RAP1GAP were also evaluated using western blotting and real-time PCR, respectively.

Results: The hyper-methylation rates of CpG24 and CpG74a in the MTC samples were considerably higher than the controls (83% versus 15% and 74% versus 17%, respectively; P<0.001). The methylation/unmethylation ratio of CpG74a , and CpG24 was considerably higher than the controls (P<0.001). The methylation/unmethylation ratio of CpG24 in the benign nodules was also considerably greater than the controls (P<0.001). The mRNA expression and the protein level of RAP1GAP in the MTC group were considerably lower than the controls (P=0.005 and P=0.035, respectively). In the MTC group, aberrant methylation of CpG74a and CpG24 was significantly correlated with decreasing expression of the Rap1Gap gene (R2 : 0.23; P=0.032 and R2 : 0.56; P=0.001, respectively).

Conclusion: Hyper-methylation in CpG24 and CpG74a and decreasing expression of RAP1GAP can be considered as diagnostic biomarkers for MTC.



Cite this article as: Faam B, Ghadiri AA, Ghaffari MA, Totonchi M, Amouzegar A, Azizi F, et al. Cpg island methylation of the rap1gap gene in medullary thyroid cancer. Arch Iran Med. 2022;25(3):171-177. doi: 10.34172/aim.2022.29
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Submitted: 26 Oct 2020
Revision: 31 Jan 2021
Accepted: 07 Feb 2021
ePublished: 01 Mar 2022
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