TET3- and OGT-Dependent Expression of Genes Involved in Epithelial-Mesenchymal Transition in Endometrial Cancer
TET3 is a member of the TET (ten-eleven translocation) proteins family that catalyzes the conversion of the 5-methylcytosine into 5-hydroxymethylcytosine. TET proteins can also affect chromatin modifications and gene expression independently of their enzymatic activity via interactions with other pr...
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| author | Piotr Ciesielski Paweł Jóźwiak Ewa Forma Anna Krześlak |
| author_facet | Piotr Ciesielski Paweł Jóźwiak Ewa Forma Anna Krześlak |
| author_sort | Piotr Ciesielski |
| collection | DOAJ |
| description | TET3 is a member of the TET (ten-eleven translocation) proteins family that catalyzes the conversion of the 5-methylcytosine into 5-hydroxymethylcytosine. TET proteins can also affect chromatin modifications and gene expression independently of their enzymatic activity via interactions with other proteins. O-GlcNAc transferase (OGT), the enzyme responsible for modification of proteins via binding of <i>N</i>-acetylglucosamine residues, is one of the proteins whose action may be dependent on TET3. Here, we demonstrated that in endometrial cancer cells both TET3 and OGT affected the expression of genes involved in epithelial to mesenchymal transition (EMT), i.e., <i>FOXC1</i>, <i>TWIST1</i>, and <i>ZEB1</i>. OGT overexpression was caused by an increase in <i>TWIST1</i> and <i>ZEB1</i> levels in HEC-1A and Ishikawa cells, which was associated with increased O-GlcNAcylation of histone H2B and trimethylation of H3K4. The TET3 had the opposite effect on gene expressions and histone modifications. OGT and TET3 differently affected <i>FOXC1</i> expression and the migratory potential of HEC-1A and Ishikawa cells. Analysis of gene expressions in cancer tissue samples from endometrial cancer patients confirmed the association between OGT or TET3 and EMT genes. Our results contribute to the knowledge of the role of the TET3/OGT relationship in the complex mechanism supporting endometrial cancer progression. |
| first_indexed | 2024-03-10T03:57:43Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:57:43Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a67d46e3db0c45f48bc9a7fb5cbe8bc82023-11-23T08:43:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241323910.3390/ijms222413239TET3- and OGT-Dependent Expression of Genes Involved in Epithelial-Mesenchymal Transition in Endometrial CancerPiotr Ciesielski0Paweł Jóźwiak1Ewa Forma2Anna Krześlak3Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Łódź, PolandDepartment of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Łódź, PolandDepartment of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Łódź, PolandDepartment of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Łódź, PolandTET3 is a member of the TET (ten-eleven translocation) proteins family that catalyzes the conversion of the 5-methylcytosine into 5-hydroxymethylcytosine. TET proteins can also affect chromatin modifications and gene expression independently of their enzymatic activity via interactions with other proteins. O-GlcNAc transferase (OGT), the enzyme responsible for modification of proteins via binding of <i>N</i>-acetylglucosamine residues, is one of the proteins whose action may be dependent on TET3. Here, we demonstrated that in endometrial cancer cells both TET3 and OGT affected the expression of genes involved in epithelial to mesenchymal transition (EMT), i.e., <i>FOXC1</i>, <i>TWIST1</i>, and <i>ZEB1</i>. OGT overexpression was caused by an increase in <i>TWIST1</i> and <i>ZEB1</i> levels in HEC-1A and Ishikawa cells, which was associated with increased O-GlcNAcylation of histone H2B and trimethylation of H3K4. The TET3 had the opposite effect on gene expressions and histone modifications. OGT and TET3 differently affected <i>FOXC1</i> expression and the migratory potential of HEC-1A and Ishikawa cells. Analysis of gene expressions in cancer tissue samples from endometrial cancer patients confirmed the association between OGT or TET3 and EMT genes. Our results contribute to the knowledge of the role of the TET3/OGT relationship in the complex mechanism supporting endometrial cancer progression.https://www.mdpi.com/1422-0067/22/24/13239endometrial cancerTET proteinsO-GlcNAc transferase<i>TWIST1</i><i>ZEB1</i><i>FOXC1</i> |
| spellingShingle | Piotr Ciesielski Paweł Jóźwiak Ewa Forma Anna Krześlak TET3- and OGT-Dependent Expression of Genes Involved in Epithelial-Mesenchymal Transition in Endometrial Cancer International Journal of Molecular Sciences endometrial cancer TET proteins O-GlcNAc transferase <i>TWIST1</i> <i>ZEB1</i> <i>FOXC1</i> |
| title | TET3- and OGT-Dependent Expression of Genes Involved in Epithelial-Mesenchymal Transition in Endometrial Cancer |
| title_full | TET3- and OGT-Dependent Expression of Genes Involved in Epithelial-Mesenchymal Transition in Endometrial Cancer |
| title_fullStr | TET3- and OGT-Dependent Expression of Genes Involved in Epithelial-Mesenchymal Transition in Endometrial Cancer |
| title_full_unstemmed | TET3- and OGT-Dependent Expression of Genes Involved in Epithelial-Mesenchymal Transition in Endometrial Cancer |
| title_short | TET3- and OGT-Dependent Expression of Genes Involved in Epithelial-Mesenchymal Transition in Endometrial Cancer |
| title_sort | tet3 and ogt dependent expression of genes involved in epithelial mesenchymal transition in endometrial cancer |
| topic | endometrial cancer TET proteins O-GlcNAc transferase <i>TWIST1</i> <i>ZEB1</i> <i>FOXC1</i> |
| url | https://www.mdpi.com/1422-0067/22/24/13239 |
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