Related Experiment Video
Updated: Nov 16, 2025
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
NOL4 is Downregulated and Hyper-Methylated in Papillary Thyroid Carcinoma Suggesting Its Role as a Tumor Suppressor
Sara Sheikholeslami1, Fereidoun Azizi2, Asghar Ghasemi3
1Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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.
Insights
Aberrant promoter hyper-methylation of the NOL4 gene in papillary thyroid carcinoma (PTC) is linked to its downregulation, suggesting NOL4 may function as a tumor suppressor gene in PTC development.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Thyroid cancer is a prevalent malignancy, with papillary thyroid carcinoma (PTC) comprising 80% of cases.
- Epigenetic alterations, particularly DNA methylation, are implicated in cancer development by inactivating tumor suppressor genes.
Purpose of the Study:
- To investigate the expression and methylation status of the nucleolar protein 4 (NOL4) gene in PTC compared to multi-nodular goiter (MNG).
Main Methods:
- Quantitative RT-PCR was used to determine NOL4 mRNA levels.
- Methylation-sensitive high-resolution melting was employed to assess promoter methylation of the NOL4 gene across six regions (NOL4 (a) to NOL4 (f)).
Main Results:
- The NOL4 (f) region in the NOL4 promoter was significantly hypermethylated in PTC tissues compared to MNG tissues.
- NOL4 mRNA levels were downregulated in PTC cases relative to MNG cases.
- NOL4 (f) methylation and mRNA levels correlated with patient age, lymph node metastasis, and advanced disease stages.
Conclusions:
- Aberrant promoter hyper-methylation of NOL4 in PTC may contribute to its downregulation.
- The NOL4 gene shows potential as a tumor suppressor gene in papillary thyroid carcinoma.
More Related Videos
06:07Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
14:56Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies
Published on: May 6, 2022
Related Concept Videos
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
02:23Abnormal Proliferation
01:46Epigenetic Regulation
01:37Epigenetic Regulation
X-chromosome...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...