TET1 is a Tumor Suppressor That Inhibits Papillary Thyroid Carcinoma Cell Migration and Invasion

Background. Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) promoting demethylation in cells. However, the expression pattern and biologic significance of TET in papillary thyroid carcinoma (PTC) remain unclear. This study aim...

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Main Authors: Shuang Yu, Yali Yin, Shubin Hong, Siting Cao, Yanrui Huang, Shuwei Chen, Yujie Liu, Hongyu Guan, Quan Zhang, Yanbing Li, Haipeng Xiao
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2020/3909610
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author Shuang Yu
Yali Yin
Shubin Hong
Siting Cao
Yanrui Huang
Shuwei Chen
Yujie Liu
Hongyu Guan
Quan Zhang
Yanbing Li
Haipeng Xiao
author_facet Shuang Yu
Yali Yin
Shubin Hong
Siting Cao
Yanrui Huang
Shuwei Chen
Yujie Liu
Hongyu Guan
Quan Zhang
Yanbing Li
Haipeng Xiao
author_sort Shuang Yu
collection DOAJ
description Background. Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) promoting demethylation in cells. However, the expression pattern and biologic significance of TET in papillary thyroid carcinoma (PTC) remain unclear. This study aimed to elucidate the biological functions of TET1 and the miRNA and mRNA expression levels in PTC cells with downregulated TET1. Methods. The expression of the TET family in 49 PTC tissues and corresponding tumor-adjacent tissues, as well as PTC cell lines (BCPAP, K1, and TPC-1) and the normal thyroid epithelial cell line (Nthy-ori 3-1), were detected using quantitative real-time polymerase chain reaction. The 5hmC level was detected in PTC tissues and cell lines using immunohistochemistry and dot blot assay, respectively. After silencing the TET1 gene with siRNAs in BCPAP and TPC-1 cells, cell proliferation was detected using EdU assay. Transwell assay was used to investigate cell migration and invasion. miRNA and mRNA expression arrays were conducted in TET1-depleted BCPAP cells. Results. The expression level of TET1 decreased in PTC tissues and cell lines and was consistent with the reduction in the 5hmC level. The knockdown of the TET1 gene promoted cell migration and invasion in BCPAP cells. The expression of miR-7, miR-15/16 cluster, and let-7 family was downregulated, while the expression of let-7e was upregulated after siRNA-TET1 treatment in BCPAP cells. The expression of WNT4, FZD4, CDK6, MCF2L, and EDN1 was upregulated as potential target genes of dysregulated miRNAs. Conclusion. The study showed that TET1 dysfunction inhibited the migration and invasion of BCPAP cells and might have a potential role in the pathogenesis of PTC.
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spelling doaj-art-fbcaa83ebed9451ba2da2b26097f1e502025-02-03T06:43:45ZengWileyInternational Journal of Endocrinology1687-83371687-83452020-01-01202010.1155/2020/39096103909610TET1 is a Tumor Suppressor That Inhibits Papillary Thyroid Carcinoma Cell Migration and InvasionShuang Yu0Yali Yin1Shubin Hong2Siting Cao3Yanrui Huang4Shuwei Chen5Yujie Liu6Hongyu Guan7Quan Zhang8Yanbing Li9Haipeng Xiao10Department of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Endocrinology, Peking University Shenzhen Hospital, Shenzhen 518036, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Head and Neck Surgery, Sun Yat-Sen University Cancer Center, Guangzhou 510060, ChinaBreast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Head and Neck Surgery, Sun Yat-Sen University Cancer Center, Guangzhou 510060, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, ChinaBackground. Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) promoting demethylation in cells. However, the expression pattern and biologic significance of TET in papillary thyroid carcinoma (PTC) remain unclear. This study aimed to elucidate the biological functions of TET1 and the miRNA and mRNA expression levels in PTC cells with downregulated TET1. Methods. The expression of the TET family in 49 PTC tissues and corresponding tumor-adjacent tissues, as well as PTC cell lines (BCPAP, K1, and TPC-1) and the normal thyroid epithelial cell line (Nthy-ori 3-1), were detected using quantitative real-time polymerase chain reaction. The 5hmC level was detected in PTC tissues and cell lines using immunohistochemistry and dot blot assay, respectively. After silencing the TET1 gene with siRNAs in BCPAP and TPC-1 cells, cell proliferation was detected using EdU assay. Transwell assay was used to investigate cell migration and invasion. miRNA and mRNA expression arrays were conducted in TET1-depleted BCPAP cells. Results. The expression level of TET1 decreased in PTC tissues and cell lines and was consistent with the reduction in the 5hmC level. The knockdown of the TET1 gene promoted cell migration and invasion in BCPAP cells. The expression of miR-7, miR-15/16 cluster, and let-7 family was downregulated, while the expression of let-7e was upregulated after siRNA-TET1 treatment in BCPAP cells. The expression of WNT4, FZD4, CDK6, MCF2L, and EDN1 was upregulated as potential target genes of dysregulated miRNAs. Conclusion. The study showed that TET1 dysfunction inhibited the migration and invasion of BCPAP cells and might have a potential role in the pathogenesis of PTC.http://dx.doi.org/10.1155/2020/3909610
spellingShingle Shuang Yu
Yali Yin
Shubin Hong
Siting Cao
Yanrui Huang
Shuwei Chen
Yujie Liu
Hongyu Guan
Quan Zhang
Yanbing Li
Haipeng Xiao
TET1 is a Tumor Suppressor That Inhibits Papillary Thyroid Carcinoma Cell Migration and Invasion
International Journal of Endocrinology
title TET1 is a Tumor Suppressor That Inhibits Papillary Thyroid Carcinoma Cell Migration and Invasion
title_full TET1 is a Tumor Suppressor That Inhibits Papillary Thyroid Carcinoma Cell Migration and Invasion
title_fullStr TET1 is a Tumor Suppressor That Inhibits Papillary Thyroid Carcinoma Cell Migration and Invasion
title_full_unstemmed TET1 is a Tumor Suppressor That Inhibits Papillary Thyroid Carcinoma Cell Migration and Invasion
title_short TET1 is a Tumor Suppressor That Inhibits Papillary Thyroid Carcinoma Cell Migration and Invasion
title_sort tet1 is a tumor suppressor that inhibits papillary thyroid carcinoma cell migration and invasion
url http://dx.doi.org/10.1155/2020/3909610
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