Research Unit in Genetics and Molecular Biology-UPGEM, Faculty of Medicine of São José do Rio Preto-FAMERP, São José do Rio Preto 15090-000, Brazil.
Padre Albino University Center-UNIFIPA, Catanduva, São Paulo 15809-144, Brazil.
Genes (Basel). 2020 Aug 19;11(9):954. doi: 10.3390/genes11090954.
Deregulation of VEGFA (Vascular Endothelial Growth Factor A) and NFE2L2 (Nuclear Factor (Erythroid-derived 2)-Like 2), involved in angiogenesis and oxidative stress, can lead to thyroid cancer progression. MiR-17-5p and miR-612 are possible regulators of these genes and may promote thyroid disorders. In order to evaluate the involvement of VEGFA, NFE2L2, hsa-miR-17-5p, and hsa-miR-612 in thyroid pathology, we examined tissue samples from colloid goiter, papillary thyroid cancer (PTC), and a normal thyroid. We found higher levels of VEGFA and NFE2L2 transcripts and the VEGFA protein in goiter and PTC samples than in normal tissue. In the goiter, miR-612 and miR-17-5p levels were lower than those in PTC. Tumors, despite showing lower mRNA expression, presented higher VEGFA protein levels compared to goiter tissue. In addition, NRF2 (Nuclear Related Transcription Factor 2) protein levels in tumors were higher than those in goiter and normal tissues. Inhibition of miR-17-5p resulted in reduced NFE2L2 expression. Overall, both transcript and protein levels of NFE2L2 and VEGFA were elevated in PTC and colloid goiter. Hsa-miR-612 showed differential expression in PTC and colloid goiter, while hsa-miR-17-5p showed differential expression only in colloid goiter, suggesting that hsa-miR-17-5p may be a positive regulator of NFE2L2 expression in PTC.
VEGFA(血管内皮生长因子 A)和 NFE2L2(核因子(红细胞衍生 2)样 2)的失调,参与血管生成和氧化应激,可导致甲状腺癌的进展。miR-17-5p 和 miR-612 可能是这些基因的调节因子,可能促进甲状腺疾病。为了评估 VEGFA、NFE2L2、hsa-miR-17-5p 和 hsa-miR-612 在甲状腺病理学中的参与程度,我们检查了胶样甲状腺肿、甲状腺乳头状癌(PTC)和正常甲状腺的组织样本。我们发现,与正常组织相比,甲状腺肿和 PTC 样本中的 VEGFA 和 NFE2L2 转录本和 VEGFA 蛋白水平更高。在甲状腺肿中,miR-612 和 miR-17-5p 的水平低于 PTC。与甲状腺肿组织相比,肿瘤尽管表现出较低的 mRNA 表达,但表现出更高的 VEGFA 蛋白水平。此外,肿瘤中的 NRF2(核相关转录因子 2)蛋白水平高于甲状腺肿和正常组织。抑制 miR-17-5p 导致 NFE2L2 表达减少。总体而言,NFE2L2 和 VEGFA 的转录本和蛋白水平在 PTC 和胶样甲状腺肿中均升高。hsa-miR-612 在 PTC 和胶样甲状腺肿中表达差异,而 hsa-miR-17-5p 仅在胶样甲状腺肿中表达差异,表明 hsa-miR-17-5p 可能是 PTC 中 NFE2L2 表达的正调节剂。