VEGFA and NFE2L2 Gene Expression and Regulation by MicroRNAs in Thyroid Papillary Cancer and Colloid Goiter.

Leonardo P Stuchi,Patrícia M Biselli-Chicote,Dalisio De-Santi Neto,Nathália Maniezzo-Stuchi,Eny Maria Goloni-Bertollo,Erika C Pavarino,Tiago Henrique,Márcia Maria U Castanhole-Nunes,João Armando Padovani Neto,Ana Paula Girol

doi:10.3390/genes11090954

Leonardo P Stuchi, Patrícia M Biselli-Chicote + Show 8 more

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https://doi.org/10.3390/genes11090954

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Abstract

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 VEGFA 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.

Highlights

Colloid goiter is the most common disorder of the thyroid gland, even in non-endemic regions, and it is clinically detected in about 4% of individuals older than 30 years [1]
We aimed to evaluate mRNA and protein levels of VEGFA and NFE2L2, as well as the expression patterns of miR-17-5p and miR-612 in human papillary thyroid cancer, colloid goiter, and normal thyroid tissues, and to investigate the involvement of miR-17-5p and miR-612 in the regulation of VEGFA and NFE2L2 expression in the thyroid papillary cancer cell line (TPC-1 line)
NFE2L2 and VEGFA genes and their protein products are widely expressed in papillary thyroid cancer (PTC) and colloid goiter. miR-612 has differential expression in the thyroid tumor and colloid goiter, while miR-17 is expressed only in the goiter

Summary

Introduction

Colloid goiter is the most common disorder of the thyroid gland, even in non-endemic regions, and it is clinically detected in about 4% of individuals older than 30 years [1]. The presence of colloid goiter can indicate the beginning of malignant transformation of the thyroid leading to thyroid cancer [2,3]. Thyroid cancer is the most common endocrine neoplasia, accounting for about 1.7% of all cancer diagnoses worldwide [4], and it is the fifth most common type of cancer in women [5]. Papillary thyroid cancer (PTC) is the most common thyroid cancer, accounting for about 80% of diagnoses [6]. VEGFA (Vascular Endothelial Growth Factor A) is the first angiogenic factor induced by hypoxia and promotes proliferation, budding, migration, and formation of the endothelial matrix [8]

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