Genomic region 14q32 and thyroid cancer: biological role and clinical implication

• Grant number: 23/09650-0
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2025
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Murilo Vieira Geraldo
• Grantee: Murilo Vieira Geraldo
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Maria Ana Duhagon ; Rafael Sebastián Fort Canobra

Abstract

Papillary thyroid carcinoma (PTC) is the most prevalent histological subtype of thyroid cancer with increasing incidence worldwide. Recently, several studies have shown the abnormal expression of non coding RNAs, such as microRNAs (miRNA) and long non coding RNAs, in different types of cancer, including PTC. We have previously shown the downregulation of several miRNAs from DLK1-DIO3 genomic region, with significant impact on cancer-related processes, such as proliferation, migration and programmed cell death. In this study we aim to combine computational analyses with in vitro and in vivo assays to characterize the role of genetic and epigenetic mechanisms in the transcriptional control of the DLK1-DIO3 region in PTC and other types of cancer. We will perform: (i) the data mining of genomic and epigenomic data in different types of cancers; (ii) the comprehensive epigenetic analysis of thyroid normal and tumoral cell lines with different oncogenic backgrounds through the characterization of DNA methylation and histone modification, the pharmacological inhibition of DNA methylation and Histone acetylation and the mapping of the expression pattern of several epigenetic modulators; (iii) functional assays to access the tumor suppressor role of MEG3 and miRNAs from DLK1-DIO3 region in thyroid cancer cell lines and, finally; (vi) we will evaluate the potential of microvesicles as a delivery system of suppressors miRNAs from DLK1-DIO3 region in vitro and in vivo. We hope that the data generated by this study will shed light on the role of the miRNAs from DLK1-DIO3 in the biology of thyroid cancer and open up perspectives for the development of new adjuvant therapy for thyroid cancer. (AU)