The role of microRNAs located at DLK1-DIO3 genomic region in the biology of thyroid tumor cell

• Grant number: 17/03635-8
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2018
• End date: March 31, 2020
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Murilo Vieira Geraldo
• Grantee: Murilo Vieira Geraldo
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Papillary thyroid carcinoma (PTC) is the most prevalent histological subtype of thyroid cancer with increasing incidence worldwide. Recently, abnormal expression of microRNAs (miRNA), emerged as potential diagnostic and prognostic tools for PTC. We have previously shown the downregulation of several miRNAs from DLK1-DIO3 genomic region. This genomic region, mapped at 14q32, harbors several coding and non-coding genes, including more than 50 miRNA genes, and has been related with several types of cancer. This study aims to expand the knowledge regarding the miRNAs from DLK1-DIO3 region in PTC. By means of the oncogenic activation or pharmacological inhibition of MAPK in normal and tumor thyroid cells, respectively, we will evaluate the influence of the most prevalent oncogenic events in PTC on the expression of DLK1-DIO3-encoded miRNAs. The network of post-transcriptional regulation potentially modulated by these miRNAs will be generated using computational tools and will allow the selection of candidate miRNAs for further functional in vitro studies. Therefore, we hope to identify the miRNAs from DLK1-DIO3 region which target key members of signaling pathways and biological processes for tumorigenesis and progression of PTC, as well as evaluate the potential tumor suppressor activity for thyroid cancer therapeutics. The data generated by this study will certainly shed light on the role of the miRNAs from DLK1-DIO3 in the biology of the thyroid follicular cell and open up perspectives for the development of new adjuvant therapy for thyroid cancer. (AU)