Evaluation of the tumor suppressor role of microRNAs situated at DLK1-DIO3 genomic region in papillary thyroid carcinoma

Abstract

Papillary thyroid carcinoma (PTC) is the most prevalent histological subtype of thyroid cancer with increasing incidence worldwide. Recently, abnormal expression of microRNAs (miRNA), emerge as potential diagnostic and prognostic tools for PTC. The large scale analysis of miRNA expression of murine model of PTC revealed the down regulation of several miRNAs from DLK1-DIO3 genomic region. This genomic region, mapped at 14q32, harbors coding and non-coding genes, including more than 50 miRNA genes, many of which described as potent tumor suppressor genes. The observation that a set of Temple Syndrome (TS) patients, which bear 14q32 deletion, present increased risk of developing thyroid cancer at young age suggests that DLK1-DIO3 may harbor tumor suppressor genes important for thyroid follicular cell biology. The objective of this study is to evaluate the tumor suppressor activity of the miRNAs from DLK1-DIO3 region in vitro. To address this issue, computational analyses will be performed to select candidate miRNAs involved in the modulation of key pathways and biological processes important for cancer development and progression. Using a panel of thyroid normal and tumor cell lines, the influence of each candidate miRNA on cell proliferation and death, as well as cell migration and invasion will be analyzed. The data generated by this study will contribute with the understanding of the biological role of miRNAs from DLK1-DIO3 region in PTC and open up perspectives for the development of new therapeutic strategies. (AU)