Influence of MAPK signaling pathway on the expression of microRNAs situated at DLK1-DIO3 genomic region

• Grant number: 19/13589-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2019
• End date: July 31, 2020
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Murilo Vieira Geraldo
• Grantee: Isabelle Nogueira da Silva
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Thyroid cancer is the main type of neoplasia of the endocrine system and its incidence is increasing worldwide in the last decade. The most prevalent subtype is the papillary thyroid carcinoma (PTC), which is mainly affected by abnormal MAPK signaling activation. 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. However, the influence of the aberrant MAPK signaling on the expression of these miRNAs remains poorly understood. By means of the oncogenic activation or pharmacological inhibition of MAPK in normal and tumor thyroid cells, respectively, we aim to evaluate the influence of the most prevalent oncogenic events in PTC on the expression of DLK1-DIO3-encoded miRNAs. In both conditions, total RNA will be extracted and the influence of MAPK signaling on miRNA transcriptional levels will be detected. We expect to detect the downregulation of miRNA expression upon the oncogenic activation and restoration of their expression upon pharmacological inhibition of MAPK signaling. 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.