Functional characterization of microRNA-495-3P in Thyroid Cancer

Abstract

Thyroid Carcinoma is the most common Endocrine Cancer worldwide, with Papillary Thyroid Carcinoma (PTC) being the most prevalent histotype, comprising more than 80% of the cases. In recent years attention has been focused on the role of microRNAs (miRNAs), small non-protein encoding RNAs, in the biology of tumor cells, especially in the role of these molecules in the modulation of pathways related to tumorigenesis. Recent studies have demonstrated the decrease in the expression of miRNAs of the DLK1-DIO3 genomic region (14q32) in several types of Cancer, including PTC. Among the miRNAs located in this region, the number of those identified as tumor suppressors increases. Based on bioinformatic target prediction and gene enrichment analysis, an ongoing research project in the laboratory identified miR-495-3p as the candidate with the highest tumor suppressor potential role in PTC between more than 50 miRNAs in the DLK1-DIO3 region. The aim of the project herein is the identification and functional validation of the signaling pathways regulated by this miRNA in PTC both in vitro and in vivo. Possible targets, as well as the signaling pathways and biological processes in which the miR-495-3p might be involved will be predicted by bioinformatics. Confirmation of the miRNA:target interactions identified in silico will be accomplished by analyzing the gene expression profile of PTC cell lines overexpressing miR-495-3p contrasted with the profile of their respective controls. Functional in vitro analyzes will be performed to validate the influence of miR-495-3p on predicted signaling pathways and on the fitness of tumor cells. Finally, using xenograft models, we will evaluate the in vivo influence of miR-495-3p overexpression on the predicted targets. This project will certainly expand understanding of the role of miR-495-3p in thyroid tumor cell biology and will facilitate the development of adjuvant therapy for Thyroid Cancer. (AU)