Expression of pY397-FAK and Its miR Regulators Drive Dedifferentiation in the Thyroid Neoplasia Spectrum
Thyroid carcinomas are growing malignancies worldwide. They encompass several diagnostic categories with varying degrees of dedifferentiation. Focal adhesion kinase is involved in cellular communication and locomotion. It is regulated on a posttranscriptional level by miR-7, miR-135a, and miR-138 an...
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MDPI AG
2023-06-01
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| author | Valentina Ignjatović Jocić Jelena Janković Miljuš Tijana Išić Denčić Vladan Živaljević Svetislav Tatić Ilona Đorić Sonja Šelemetjev |
| author_facet | Valentina Ignjatović Jocić Jelena Janković Miljuš Tijana Išić Denčić Vladan Živaljević Svetislav Tatić Ilona Đorić Sonja Šelemetjev |
| author_sort | Valentina Ignjatović Jocić |
| collection | DOAJ |
| description | Thyroid carcinomas are growing malignancies worldwide. They encompass several diagnostic categories with varying degrees of dedifferentiation. Focal adhesion kinase is involved in cellular communication and locomotion. It is regulated on a posttranscriptional level by miR-7, miR-135a, and miR-138 and on a posttranslational level by autophosphorylation at Y397 (pY397-FAK). We related regulators of FAK with histologic dedifferentiation, clinicopathological factors, and differential diagnosis in the thyroid neoplasia spectrum. We classified 82 cases into 5 groups with increasing aggressiveness: healthy tissue, follicular and classical variants of papillary thyroid carcinoma (PTC), dedifferentiated PTC, and anaplastic carcinoma. MiRs were analyzed by RT-qPCR. Protein expression of pY397-FAK was analyzed by immunohistochemistry (separately in the membrane, cytoplasm, and nuclear compartment) and Western blot. All three miRs were upregulated in healthy tissue compared to malignant, while pY397-FAK was downregulated. MiRs and pY397-FAK were not mutually correlated. MiR-135a-5p was decreasing while membranous and cytoplasmic pY397-FAK increased with dedifferentiation. Neither miR correlated with clinicopathological factors. MiR-135a-5p, miR-138-5p, and membranous and cytoplasmic pY397-FAK discriminated the follicular from the classical variant of PTC. Disturbances of FAK regulation on different levels contribute to neoplastic dedifferentiation. pY397-FAK exerts its oncogenic role in the membrane and cytoplasm. Diagnostically, miRs-135a-5p, miR-138-5p, and membranous and cytoplasmic pY397-FAK differentiated between classical and follicular PTC. |
| first_indexed | 2024-03-11T01:45:13Z |
| format | Article |
| id | doaj.art-76bcb92fb02746108221045bab418d7e |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T01:45:13Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-76bcb92fb02746108221045bab418d7e2023-11-18T16:19:05ZengMDPI AGCells2073-44092023-06-011213172110.3390/cells12131721Expression of pY397-FAK and Its miR Regulators Drive Dedifferentiation in the Thyroid Neoplasia SpectrumValentina Ignjatović Jocić0Jelena Janković Miljuš1Tijana Išić Denčić2Vladan Živaljević3Svetislav Tatić4Ilona Đorić5Sonja Šelemetjev6Department of Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy—INEP, University of Belgrade, Banatska 31b, 11000 Belgrade, SerbiaDepartment of Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy—INEP, University of Belgrade, Banatska 31b, 11000 Belgrade, SerbiaDepartment of Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy—INEP, University of Belgrade, Banatska 31b, 11000 Belgrade, SerbiaCenter for Endocrine Surgery, University Clinical Center of Serbia, Doktora Subotića 13, 11000 Belgrade, SerbiaInstitute for Pathology, Faculty of Medicine, University of Belgrade, Doktora Subotića Starijeg 1, 11000 Belgrade, SerbiaDepartment of Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy—INEP, University of Belgrade, Banatska 31b, 11000 Belgrade, SerbiaDepartment of Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy—INEP, University of Belgrade, Banatska 31b, 11000 Belgrade, SerbiaThyroid carcinomas are growing malignancies worldwide. They encompass several diagnostic categories with varying degrees of dedifferentiation. Focal adhesion kinase is involved in cellular communication and locomotion. It is regulated on a posttranscriptional level by miR-7, miR-135a, and miR-138 and on a posttranslational level by autophosphorylation at Y397 (pY397-FAK). We related regulators of FAK with histologic dedifferentiation, clinicopathological factors, and differential diagnosis in the thyroid neoplasia spectrum. We classified 82 cases into 5 groups with increasing aggressiveness: healthy tissue, follicular and classical variants of papillary thyroid carcinoma (PTC), dedifferentiated PTC, and anaplastic carcinoma. MiRs were analyzed by RT-qPCR. Protein expression of pY397-FAK was analyzed by immunohistochemistry (separately in the membrane, cytoplasm, and nuclear compartment) and Western blot. All three miRs were upregulated in healthy tissue compared to malignant, while pY397-FAK was downregulated. MiRs and pY397-FAK were not mutually correlated. MiR-135a-5p was decreasing while membranous and cytoplasmic pY397-FAK increased with dedifferentiation. Neither miR correlated with clinicopathological factors. MiR-135a-5p, miR-138-5p, and membranous and cytoplasmic pY397-FAK discriminated the follicular from the classical variant of PTC. Disturbances of FAK regulation on different levels contribute to neoplastic dedifferentiation. pY397-FAK exerts its oncogenic role in the membrane and cytoplasm. Diagnostically, miRs-135a-5p, miR-138-5p, and membranous and cytoplasmic pY397-FAK differentiated between classical and follicular PTC.https://www.mdpi.com/2073-4409/12/13/1721pY397-FAKmiRsthyroid carcinomaneoplastic dedifferentiationdifferential diagnostics |
| spellingShingle | Valentina Ignjatović Jocić Jelena Janković Miljuš Tijana Išić Denčić Vladan Živaljević Svetislav Tatić Ilona Đorić Sonja Šelemetjev Expression of pY397-FAK and Its miR Regulators Drive Dedifferentiation in the Thyroid Neoplasia Spectrum Cells pY397-FAK miRs thyroid carcinoma neoplastic dedifferentiation differential diagnostics |
| title | Expression of pY397-FAK and Its miR Regulators Drive Dedifferentiation in the Thyroid Neoplasia Spectrum |
| title_full | Expression of pY397-FAK and Its miR Regulators Drive Dedifferentiation in the Thyroid Neoplasia Spectrum |
| title_fullStr | Expression of pY397-FAK and Its miR Regulators Drive Dedifferentiation in the Thyroid Neoplasia Spectrum |
| title_full_unstemmed | Expression of pY397-FAK and Its miR Regulators Drive Dedifferentiation in the Thyroid Neoplasia Spectrum |
| title_short | Expression of pY397-FAK and Its miR Regulators Drive Dedifferentiation in the Thyroid Neoplasia Spectrum |
| title_sort | expression of py397 fak and its mir regulators drive dedifferentiation in the thyroid neoplasia spectrum |
| topic | pY397-FAK miRs thyroid carcinoma neoplastic dedifferentiation differential diagnostics |
| url | https://www.mdpi.com/2073-4409/12/13/1721 |
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