Abstract
The aberrant expression of miRNAs is often correlated to tumor development. MiR-7-5p is a recently discovered downregulated miRNA in thyroid papillary carcinoma (PTC). 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. Several effectors of these pathways are indeed targets of miR-7-5p, among which EGFR and IRS2, two upstream activators. We confirmed the upregulation of IRS2 and EGFR in human PTC and showed the existence of a negative correlation between the decreased expression of miR-7-5p and the increased expression of IRS2 or EGFR. Our results thus support a tumor-suppressor activity of miR-7-5p. The decreased expression of miR-7-5p during PTC tumorigenesis might give the cells a proliferative advantage and delivery of miR-7-5p may represent an innovative approach for therapy.
Highlights
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
MiR-7-5p is downregulated in papillary thyroid carcinomas and in thyroid derived cell lines
MiR-7-5p is downregulated in Papillary thyroid cancer (PTC) samples compared to normal tissues and its expression is even significantly more downregulated in lymph node metastases (Figure 1A)
Summary
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. All the theoretical targets of a miRNA can be defined in silico by using bioinformatic prediction models [1] Because of their global cellular role, miRNAs are involved in a large amount of biological processes and in many human diseases including cancer. The incidence of thyroid cancers has been reported to increase by over 5% annually [10]. Until a few years ago, PTC was characterized as a cancer presenting essentially upregulated miRNAs in multiple human cancers a general downregulation of miRNAs is generally observed [11,12,13,14,15]. With the emergence of the Generation Sequencing tools, a lot of downregulated miRNAs associated to PTC have been reported [16,17,18]
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