Department of Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Banatska 31b, 11000 Belgrade, Serbia.
Center for Endocrine Surgery, University Clinical Center of Serbia, Doktora Subotića 13, 11000 Belgrade, Serbia.
Cells. 2023 Jun 26;12(13):1721. doi: 10.3390/cells12131721.
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.
甲状腺癌是全球范围内不断增长的恶性肿瘤。它们包含几个具有不同去分化程度的诊断类别。粘着斑激酶参与细胞通讯和运动。它在转录后水平上受到 miR-7、miR-135a 和 miR-138 的调节，在翻译后水平上受到 Y397 自身磷酸化（pY397-FAK）的调节。我们将粘着斑激酶的调节剂与甲状腺肿瘤谱中的组织学去分化、临床病理因素和鉴别诊断联系起来。我们将 82 例病例分为 5 组，侵袭性逐渐增强：健康组织、滤泡型和经典型甲状腺乳头状癌（PTC）、去分化型 PTC 和间变性癌。通过 RT-qPCR 分析 miR 的表达。通过免疫组织化学（分别在膜、细胞质和核区室）和 Western blot 分析 pY397-FAK 的蛋白表达。与恶性组织相比，所有三种 miR 在健康组织中均上调，而 pY397-FAK 下调。miR 与 pY397-FAK 之间没有相互关联。miR-135a-5p 下调，而膜性和细胞质 pY397-FAK 随着去分化而增加。miR 与临床病理因素均无相关性。miR-135a-5p、miR-138-5p 和膜性及细胞质 pY397-FAK 可区分滤泡型和经典型 PTC。粘着斑激酶在不同水平的调节紊乱有助于肿瘤的去分化。pY397-FAK 在膜和细胞质中发挥其致癌作用。在诊断方面，miR-135a-5p、miR-138-5p 和膜性及细胞质 pY397-FAK 可区分经典型和滤泡型 PTC。
Zotero 插件