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NOL4 is Downregulated and Hyper-Methylated in Papillary Thyroid Carcinoma Suggesting Its Role as a Tumor Suppressor Gene

BACKGROUND: Thyroid cancer is the fourth most common cancer in the world. Papillary thyroid carcinoma (PTC) accounts for 80% of all types of thyroid neoplasm. Epigenetic alterations such as DNA methylation are known as the main cause of different types of cancers through inactivation of tumor suppre...

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Autores principales: Sheikholeslami, Sara, Azizi, Fereidoun, Ghasemi, Asghar, Alibakhshi, Abbas, Parsa, Hossein, Tavangar, Seyed Mohammad, Shivaee, Setareh, Zarif Yeganeh, Marjan, Hedayati, Mehdi, Teimoori-Toolabi, Ladan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Kowsar 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887463/
https://www.ncbi.nlm.nih.gov/pubmed/33613681
http://dx.doi.org/10.5812/ijem.108510
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author Sheikholeslami, Sara
Azizi, Fereidoun
Ghasemi, Asghar
Alibakhshi, Abbas
Parsa, Hossein
Tavangar, Seyed Mohammad
Shivaee, Setareh
Zarif Yeganeh, Marjan
Hedayati, Mehdi
Teimoori-Toolabi, Ladan
author_facet Sheikholeslami, Sara
Azizi, Fereidoun
Ghasemi, Asghar
Alibakhshi, Abbas
Parsa, Hossein
Tavangar, Seyed Mohammad
Shivaee, Setareh
Zarif Yeganeh, Marjan
Hedayati, Mehdi
Teimoori-Toolabi, Ladan
author_sort Sheikholeslami, Sara
collection PubMed
description BACKGROUND: Thyroid cancer is the fourth most common cancer in the world. Papillary thyroid carcinoma (PTC) accounts for 80% of all types of thyroid neoplasm. Epigenetic alterations such as DNA methylation are known as the main cause of different types of cancers through inactivation of tumor suppressor genes. OBJECTIVES: In the present study, the expression and methylation of suggested gene namely nucleolar protein 4 (NOL4) in PTC in comparison to multi nodular goiter (MNG) have been studied. METHODS: Forty-one patients with PTC and 38 patients affected by MNG were recruited. 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 NOL4 while methylation-sensitive high resolution methylation was applied for assessing the methylation status with designing six pairs primers for six regions on gene promoter which were named from NOL4 (a) to NOL4 (f). RESULTS: Methylation assessment of 81 CpG islands in the promoter region of NOL4 gene revealed that NOL4 (f), the nearest region to the start codon, was significantly hypermethylated in PTC cases compared to MNG cases. NOL4 level in PTC cases in comparison with MNG cases were downregulated. The methylation status and mRNA level of NOL4 (f) were associated with age of diagnosis (Age of the patient at the time of diagnosis), lymph node metastasis, and advanced stages of disease. CONCLUSIONS: These data suggested an aberrant promoter hyper-methylation of NOL4 in PTC cases may be linked with its downregulation. Therefore, NOL4 gene can be proposed as a potential tumor suppressor gene in PTC tissues.
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spelling pubmed-78874632021-02-19 NOL4 is Downregulated and Hyper-Methylated in Papillary Thyroid Carcinoma Suggesting Its Role as a Tumor Suppressor Gene Sheikholeslami, Sara Azizi, Fereidoun Ghasemi, Asghar Alibakhshi, Abbas Parsa, Hossein Tavangar, Seyed Mohammad Shivaee, Setareh Zarif Yeganeh, Marjan Hedayati, Mehdi Teimoori-Toolabi, Ladan Int J Endocrinol Metab Research Article BACKGROUND: Thyroid cancer is the fourth most common cancer in the world. Papillary thyroid carcinoma (PTC) accounts for 80% of all types of thyroid neoplasm. Epigenetic alterations such as DNA methylation are known as the main cause of different types of cancers through inactivation of tumor suppressor genes. OBJECTIVES: In the present study, the expression and methylation of suggested gene namely nucleolar protein 4 (NOL4) in PTC in comparison to multi nodular goiter (MNG) have been studied. METHODS: Forty-one patients with PTC and 38 patients affected by MNG were recruited. 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 NOL4 while methylation-sensitive high resolution methylation was applied for assessing the methylation status with designing six pairs primers for six regions on gene promoter which were named from NOL4 (a) to NOL4 (f). RESULTS: Methylation assessment of 81 CpG islands in the promoter region of NOL4 gene revealed that NOL4 (f), the nearest region to the start codon, was significantly hypermethylated in PTC cases compared to MNG cases. NOL4 level in PTC cases in comparison with MNG cases were downregulated. The methylation status and mRNA level of NOL4 (f) were associated with age of diagnosis (Age of the patient at the time of diagnosis), lymph node metastasis, and advanced stages of disease. CONCLUSIONS: These data suggested an aberrant promoter hyper-methylation of NOL4 in PTC cases may be linked with its downregulation. Therefore, NOL4 gene can be proposed as a potential tumor suppressor gene in PTC tissues. Kowsar 2020-10-19 /pmc/articles/PMC7887463/ /pubmed/33613681 http://dx.doi.org/10.5812/ijem.108510 Text en Copyright © 2020, International Journal of Endocrinology and Metabolism http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
spellingShingle Research Article
Sheikholeslami, Sara
Azizi, Fereidoun
Ghasemi, Asghar
Alibakhshi, Abbas
Parsa, Hossein
Tavangar, Seyed Mohammad
Shivaee, Setareh
Zarif Yeganeh, Marjan
Hedayati, Mehdi
Teimoori-Toolabi, Ladan
NOL4 is Downregulated and Hyper-Methylated in Papillary Thyroid Carcinoma Suggesting Its Role as a Tumor Suppressor Gene
title NOL4 is Downregulated and Hyper-Methylated in Papillary Thyroid Carcinoma Suggesting Its Role as a Tumor Suppressor Gene
title_full NOL4 is Downregulated and Hyper-Methylated in Papillary Thyroid Carcinoma Suggesting Its Role as a Tumor Suppressor Gene
title_fullStr NOL4 is Downregulated and Hyper-Methylated in Papillary Thyroid Carcinoma Suggesting Its Role as a Tumor Suppressor Gene
title_full_unstemmed NOL4 is Downregulated and Hyper-Methylated in Papillary Thyroid Carcinoma Suggesting Its Role as a Tumor Suppressor Gene
title_short NOL4 is Downregulated and Hyper-Methylated in Papillary Thyroid Carcinoma Suggesting Its Role as a Tumor Suppressor Gene
title_sort nol4 is downregulated and hyper-methylated in papillary thyroid carcinoma suggesting its role as a tumor suppressor gene
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887463/
https://www.ncbi.nlm.nih.gov/pubmed/33613681
http://dx.doi.org/10.5812/ijem.108510
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