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Oncotarget: Inhibiting thyroid cell proliferation by targeting signaling pathways


Oncotarget published "MiR-7-5p inhibits thyroid cell proliferation by targeting the EGFR/MAPK and IRS2/PI3K signaling pathways" which reported that MiR-7-5p is a recently discovered down regulated miRNA in thyroid papillary carcinoma.

The goal of this project was to characterize its functional role in thyroid tumorigenesis and to identify the targeted modulated pathways. MiR-7-5p overexpression following transfection in TPC1 and HT-ori3 cells decreased proliferation of the two thyroid cell lines. Analysis of global transcriptome modifications showed that miR-7-5p inhibits thyroid cell proliferation by modulating the MAPK and PI3K signaling pathways which are both necessary for normal thyroid proliferation and play central roles in PTC tumorigenesis.

Dr. Carine Maenhaut from The Université libre de Bruxelles said, "MiRNAs are small endogenous single-strand RNA molecules of ~23 nucleotides in length, described as essential players in the regulation of gene expression by targeting coding mRNAs."

Because of their global cellular role, miRNAs are involved in a large amount of biological processes but also in many human diseases including cancer. Several studies have shown that many miRNAs are overexpressed or downregulated in tumor tissues compared to adjacent normal tissues, and some evidence support their incidence in tumor initiation and/or progression. Thyroid cancer is the most prevalent endocrine cancer by constituting almost 93% of cancers associated to this system. During the past decade, the incidence of thyroid cancers has been reported to increase by over 5% annually.

Thyroid cancer is the most prevalent endocrine cancer by constituting almost 93% of cancers associated to this system

Papillary thyroid cancer corresponds to approximately 85% of malignant thyroid cancers. Until a few years ago, PTC was characterized as a cancer presenting essentially upregulated miRNAs although in multiple human cancers a general downregulation of miRNAs is generally observed.

Nevertheless, with the emergence of the Next Generation Sequencing tools, a lot of downregulated miRNAs associated to PTC have been reported. Indeed, miR-7-5p was shown to inhibit proliferation in lung carcinoma and glioblastoma, to inhibit migration and invasion in melanoma, and to promote proliferation and migration in lung carcinoma, skin epithelial cells and renal cancer.

An active role of this miRNAs in PTC tumorigenesis is thereby conceivable. These data suggest that miR-7-5p inhibits thyroid cell proliferation by targeting the MAPK and PI3K signaling pathways.

Figure 8: Dereregulation of miR-7-5p, IRS2 and EGFR according to PTC aggressivity. THCA study from TCGA database analyses of miR-7-5p, IRS2 and EGFR expression in BRAFV600E negative (grey) and positive (black) PTC. Results are expressed as min-to-max box plots. Mann-Whitney test was used to define statistically significant modulation; ***p < 0.001.

The Maenhaut Research Team concluded in their Oncotarget Research Output, "we have evaluated the functional role of miR-7-5p in thyroid cells and shown that this miRNA negatively regulates the expression of several signaling targets active in the MAPK and PI3K/Akt signaling pathways. Hence, its decreased expression during PTC tumorigenesis could give the cells a proliferative advantage. Given the central roles of the MAPK and PI3K/Akt pathways in PTC tumorigenesis, delivery of miR-7-5p may represent an innovative approach for therapy, especially for high proliferative PTC recurrences. Future research on miR-7-5p will allow to define its potential therapeutic application by using already available delivery systems like cell-penetrating peptides, liposomes, micelles, and polymeric nanoparticles"

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DOI - https://doi.org/10.18632/oncotarget.28030

Full text - https://www.oncotarget.com/article/28030/text/

Correspondence to - Carine Maenhaut - carine.maenhaut@ulb.be

Keywords - miRNA, papillary thyroid carcinoma, IRS2, MAPK, PI3K

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