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Published on: August 23, 2019
TET1 is a Tumor Suppressor That Inhibits Papillary Thyroid Carcinoma Cell Migration and Invasion
Shuang Yu1, Yali Yin2, Shubin Hong1
1Department of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
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.
Insights
Ten-eleven translocation (TET) enzymes, crucial for DNA demethylation, are downregulated in papillary thyroid carcinoma (PTC). TET1 dysfunction inhibits cancer cell migration and invasion, suggesting its role in PTC development.
Area of Science:
- Molecular Biology
- Epigenetics
- Oncology
Background:
- Ten-eleven translocation (TET) enzymes regulate DNA demethylation by oxidizing 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC).
- The expression and function of TET enzymes, particularly TET1, in papillary thyroid carcinoma (PTC) are not well understood.
- This study investigates the role of TET1 in PTC pathogenesis and its impact on miRNA and mRNA expression.
Purpose of the Study:
- To determine the expression levels of TET family genes in PTC tissues and cell lines.
- To investigate the functional impact of TET1 downregulation on PTC cell proliferation, migration, and invasion.
- To identify miRNA and mRNA expression changes in PTC cells with reduced TET1 levels.
Main Methods:
- Quantitative real-time PCR was used to assess TET gene expression in PTC tissues and cell lines.
- Immunohistochemistry and dot blot assays measured 5hmC levels.
- siRNA-mediated TET1 knockdown was performed, followed by EdU, Transwell, and miRNA/mRNA array analyses.
Main Results:
- TET1 expression and 5hmC levels were significantly reduced in PTC tissues and cell lines compared to normal controls.
- TET1 knockdown inhibited PTC cell proliferation, migration, and invasion.
- miRNA and mRNA expression profiling revealed upregulation of potential target genes including WNT4, FZD4, CDK6, MCF2L, and EDN1.
Conclusions:
- TET1 dysfunction is associated with reduced 5hmC levels and plays an inhibitory role in PTC cell migration and invasion.
- TET1 may be a potential therapeutic target and biomarker in papillary thyroid carcinoma.
- Altered miRNA and mRNA expression profiles in TET1-depleted PTC cells highlight potential regulatory pathways in tumorigenesis.
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