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

2020 ◽  
Vol 18 (4) ◽  
Author(s):  
Sara Sheikholeslami ◽  
Fereidoun Azizi ◽  
Asghar Ghasemi ◽  
Abbas Alibakhshi ◽  
Hossein Parsa ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Tumor Suppressor ◽  
Thyroid Carcinoma ◽  
Tumor Suppressor Gene ◽  
Mrna Level ◽  
Methylation Status ◽  
Nodular Goiter ◽  
Suppressor Gene ◽  
Start Codon ◽  
Papillary Thyroid

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.

scholarly journals Characterization of the novel tumor-suppressor gene CCDC67 in papillary thyroid carcinoma

Oncotarget ◽  
2015 ◽  
Vol 7 (5) ◽  
pp. 5830-5841 ◽  
Author(s):  
De-Tao Yin ◽  
Jianhui Xu ◽  
Mengyuan Lei ◽  
Hongqiang Li ◽  
Yongfei Wang ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Tumor Suppressor ◽  
Thyroid Carcinoma ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
The Novel ◽  
Papillary Thyroid

Tumor Suppressor Gene Allelic Loss Profiles of the Variants of Papillary Thyroid Carcinoma

2004 ◽  
Vol 13 (1) ◽  
pp. 41-46 ◽  
Author(s):  
Jennifer L. Hunt ◽  
Melissa Fowler ◽  
Deren Lomago ◽  
Laura Niehouse ◽  
Eizaburo Sasatomi ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Tumor Suppressor ◽  
Thyroid Carcinoma ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Allelic Loss ◽  
Papillary Thyroid

Clinicopathological Roles of Alterations of Tumor Suppressor Gene p16 in Papillary Thyroid Carcinoma

2006 ◽  
Vol 14 (5) ◽  
pp. 1772-1779 ◽  
Author(s):  
Alfred King Yin Lam ◽  
Chung Yau Lo ◽  
Pauline Leung ◽  
Brian Hung Hin Lang ◽  
Wai Fun Chan ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Tumor Suppressor ◽  
Thyroid Carcinoma ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Papillary Thyroid

scholarly journals A novel tumor suppressor gene NCOA5 is correlated with progression in papillary thyroid carcinoma

2018 ◽  
Vol Volume 11 ◽  
pp. 307-311 ◽  
Author(s):  
Zhou-Ci Zheng ◽  
Qing-Xuan Wang ◽  
Wei Zhang ◽  
Xiao-Hua Zhang ◽  
Du-Ping Huang
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Tumor Suppressor ◽  
Thyroid Carcinoma ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Papillary Thyroid

Methylation of p73 Gene is Associated with Increased Risk of Papillary Thyroid Cancer

2019 ◽  
Vol 9 (5) ◽  
pp. 694-699
Author(s):  
Xiaojie Gao ◽  
Zhenyu Hou ◽  
Shucheng Wang
Keyword(s):  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Papillary Thyroid Cancer ◽  
Methylation Level ◽  
Mrna Level ◽  
Suppressor Gene ◽  
Papillary Thyroid ◽  
Increased Risk ◽  
P73 Gene

This study aimed to investigate the association between methylation in the promoter region of the p73 gene and the clinical features papillary thyroid cancer. Forty-two pairs of papillary thyroid cancer and corresponding paracancerous tissues and blood samples from January to June 2015 were enrolled in this study. The methylation level of the p73 gene and p73 mRNA level were detected by methylation-specific PCR and quantitative reverse transcription-PCR. The correlation between the methylation level of p73 gene and p73 mRNA level was analyzed. The methylation status of p73 and p16 in plasma were also detected, and the correlation between them was analyzed. The results showed that p73 methylation was found at CG sites in 28 cancer tissues, which mainly located at positions 21, 22, 23 CG sites, but methylation was not identified at CG sites in paracancerous tissues (P < 0.01). The methylation level of the p73 gene was negatively correlated with p73 mRNA level (P < 0.01). Methylation of p73 gene was correlated with lymph node metastasis, but not age, sex, clinical stage of the patients. Methylation of p73 in plasma was correlated with methylation of tumor suppressor gene p16, which increased the risk of papillary thyroid cancer. In conclusion, we found that hypermethylation of the p73 gene is associated with the development and metastasis of papillary thyroid cancer, which may be suggested as a new candidate tumor suppressor gene in papillary thyroid cancer.

Methylation status of HOXB4 gene in papillary thyroid carcinoma

2014 ◽  
Author(s):  
Andreea Brehar ◽  
Camelia Procopiuc ◽  
Diana Paun ◽  
Dana Manda ◽  
Sabina Oros ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Methylation Status ◽  
Papillary Thyroid

Identification of Differentially Expressed Genes Associated with Papillary Thyroid Carcinoma

2020 ◽  
Vol 23 (6) ◽  
pp. 546-553
Author(s):  
Hongyuan Cui ◽  
Mingwei Zhu ◽  
Junhua Zhang ◽  
Wenqin Li ◽  
Lihui Zou ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Mrna Level ◽  
Thyroid Tissue ◽  
Differentially Expressed ◽  
Thyroid Tumors ◽  
Papillary Thyroid

Objective: Next-generation sequencing (NGS) was performed to identify genes that were differentially expressed between normal thyroid tissue and papillary thyroid carcinoma (PTC). Materials & Methods: Six candidate genes were selected and further confirmed with quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry in samples from 24 fresh thyroid tumors and adjacent normal tissues. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to investigate signal transduction pathways of the differentially expressed genes. Results: In total, 1690 genes were differentially expressed between samples from patients with PTC and the adjacent normal tissue. Among these, SFRP4, ZNF90, and DCN were the top three upregulated genes, whereas KIRREL3, TRIM36, and GABBR2 were downregulated with the smallest p values. Several pathways were associated with the differentially expressed genes and involved in cellular proliferation, cell migration, and endocrine system tumor progression, which may contribute to the pathogenesis of PTC. Upregulation of SFRP4, ZNF90, and DCN at the mRNA level was further validated with RT-PCR, and DCN expression was further confirmed with immunostaining of PTC samples. Conclusion: These results provide new insights into the molecular mechanisms of PTC. Identification of differentially expressed genes should not only improve the tumor signature for thyroid tumors as a diagnostic biomarker but also reveal potential targets for thyroid tumor treatment.

scholarly journals Tumor Suppressor LKB1 Inhibits Activation of Signal Transducer and Activator of Transcription 3 (STAT3) by Thyroid Oncogenic Tyrosine Kinase Rearranged in Transformation (RET)/Papillary Thyroid Carcinoma (PTC)

2007 ◽  
Vol 21 (12) ◽  
pp. 3039-3049 ◽  
Author(s):  
Dong Wook Kim ◽  
Hyo Kyun Chung ◽  
Ki Cheol Park ◽  
Jung Hwan Hwang ◽  
Young Suk Jo ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Tumor Suppressor ◽  
Thyroid Carcinoma ◽  
Malignant Tumors ◽  
Kinase Domain ◽  
Signal Transducer ◽  
Papillary Thyroid ◽  
Loss Of Function ◽  
Amino Acid Region ◽  
Transcription 3

Abstract The tumor suppressor LKB1 (STK11) is a cytoplasmic/nuclear serine/threonine kinase, defects in which cause Peutz-Jeghers syndrome (PJS) in humans and animals. Recent studies showed that loss of function of LKB1 is associated with sporadic forms of lung, pancreatic, and ovarian cancer. In cancer cells, LKB1 is inactivated by two mechanisms: mutations in its central kinase domain or complete loss of LKB1 expression. Inactivation of LKB1 is associated with progression of PJS and transformation of benign polyps into malignant tumors. This study examines the effect of LKB1 on regulation of STAT3 and expression of transcriptional targets of STAT3. The results show that LKB1 inhibits rearranged in transformation (RET)/papillary thyroid carcinoma (PTC)-dependent activation of signal transducer and activator of transcription 3 (STAT3), which is mediated by phosphorylation of STAT3 tyrosine 705 by RET/PTC. Suppression of STAT3 transactivation by LKB1 requires the kinase domain but not the kinase activity of LKB1. The centrally located kinase domain of LKB1 is an approximately 260-amino-acid region that binds to the linker domain of STAT3. Chromatin immunoprecipitation studies indicate that expression of LKB1 reduces the binding of STAT3 to its target promoters and suppresses STAT3-mediated expression of Cyclin D1, VEGF, and Bcl-xL. Knockdown of LKB1 by specific small interfering RNA led to an increase in STAT3 transactivation activity and promoted cell proliferation in the presence of RET/PTC. Thus, this study suggests that LKB1 suppresses tumor growth by inhibiting RET/PTC-dependent activation of oncogenic STAT3.

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