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

Shuang Yu; Yali Yin; Shubin Hong; Siting Cao; Yanrui Huang; Shuwei Chen; Yujie Liu; Hongyu Guan; Quan Zhang; Yanbing Li; Haipeng Xiao

doi:10.1155/2020/3909610

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

Int J Endocrinol. 2020 Feb 8:2020:3909610. doi: 10.1155/2020/3909610. eCollection 2020.

Authors

Shuang Yu¹, Yali Yin², Shubin Hong¹, Siting Cao¹, Yanrui Huang¹, Shuwei Chen^{3

4}, Yujie Liu⁵, Hongyu Guan¹, Quan Zhang³, Yanbing Li¹, Haipeng Xiao¹

Affiliations

¹ Department of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
² Department of Endocrinology, Peking University Shenzhen Hospital, Shenzhen 518036, China.
³ Department of Head and Neck Surgery, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China.
⁴ State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.
⁵ Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.

Abstract

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 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. 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.