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

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.

The Keap1/Nrf2 Signaling Pathway in the Thyroid—2020 Update

“…Somatic mutations in KEAP1, NFE2L2, or other Nrf2 pathway components were not reported in this study, which is not surprising, knowing that the frequency of such mutations in thyroid cancer is lower than in other cancer types with activated Nrf2 signaling [64,65], and given the small sample size of the specific study [66]. Another study found higher Nrf2 mRNA levels and Nrf2 protein abundance in PTC samples compared to normal tissues [67]; of note, Nrf2 is known to induce the transcription of its own gene (at least in the mouse), via an ARE element in the gene promoter [68]. Further, the same study showed that inhibition of microRNA miR-17-5p in a PTC cell line decreased Nrf2 mRNA expression levels [67].…”

“…Another study found higher Nrf2 mRNA levels and Nrf2 protein abundance in PTC samples compared to normal tissues [67]; of note, Nrf2 is known to induce the transcription of its own gene (at least in the mouse), via an ARE element in the gene promoter [68]. Further, the same study showed that inhibition of microRNA miR-17-5p in a PTC cell line decreased Nrf2 mRNA expression levels [67]. Another study found increased expression of the long non-coding RNA lung cancer associated transcript 1 (LUCAT1) in PTC, as well as a positive correlation between LUCAT1 expression levels and unfavorable clinicopathological parameters [69].…”

Circular RNA profiling reveals a potential role of hsa_circ_IPCEF1 in papillary thyroid carcinoma

“…The molecular predictors of preoperative diagnostics and accurate treatment for PTC are poorly defined. Although studies have focused on mRNA transcripts and non-coding RNAs as potential PTC markers, the expression profiles and roles of circRNAs in PTC remain to be elucidated (49)(50)(51)(52). By contrast with recent studies in circRNA screening in PTC tissues, the present study validated seven dysregulated circRNAs (three upregulated and four downregulated) in whole blood from PTC subjects, which were found to be more suitable for biomarker detection in the future (53,54).…”

Development and Validation of a Novel Gene Signature for Predicting the Prognosis by Identifying m5C Modification Subtypes of Cervical Cancer

“…In multiple myeloma, high expression of FNDC3A can lead to ROS accumulation, ATP deficiency and cell death in multiple myeloma cells. VEGFA can be used as a prognostic biomarker for head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, glioblastoma and papillary thyroid carcinoma ( He et al, 2020 ; Stuchi et al, 2020 ; Yang et al, 2020 ; Zheng and Tao, 2020 ). Downregulation of VEGFA expression can inhibit the proliferation, angiogenesis and metastasis of osteosarcoma cells, ovarian cancer and lung squamous cell carcinoma ( Chen et al, 2020a ; Chen et al, 2020b ; Li et al, 2020 ; Qin et al, 2020 ).…”