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| Author(s): |
Letícia Ferreira Alves
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2023-10-17 |
| Examining board members: |
Murilo Vieira Geraldo;
Caroline Serrano Nascimento;
Helder Takashi Imoto Nakaya;
Hernandes Faustino de Carvalho;
Mariana Maschietto
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| Advisor: | Murilo Vieira Geraldo |
| 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. Recent research has focused on the roles of microRNAs (miRNAs) in tumor biology, particularly their impact on carcinogenesis pathways. Studies have revealed reduced DLK1-DIO3-derived miRNA expression in different cancer types, including PTC, with several of these miRNAs identified as tumor suppressors. Among these miRNAs, miR-495-3p emerged as a potential tumor suppressor in PTC through bioinformatic analysis conducted by our group. In the first chapter of this study, we explored miR-495-3p's role in PTC, predicting its targets and associated pathways, confirming its influence on tumor cell fitness, and modulating the expression of key genes. These findings underscore miR-495- 3p's significance in regulating processes and pathways tied to tumor development and progression. Building upon our findings in Chapter I, Chapter II explores the epigenetic mechanisms controlling the expression of the DLK1-DIO3 genomic region in thyroid malignancies. Analysis of DNA methylation data from the region revealed differences in the region's methylation status between normal and malignant cells. We identified a shift in the methylation of CpG islands on the MEG3 differentially methylated region (MEG3-DMR) that may be responsible for the region's global downregulation in the context of thyroid tumors. Additionally, histone modifications showed significant changes in one cell line. Pharmacological demethylation and HDAC inhibition restored MEG3 expression, reinforcing the impact of methylation and histone acetylation in thyroid cancer development. In summary, our work underscores the significance of miR-495-3p in regulating critical processes in PTC and sheds light on the epigenetic mechanisms responsible for the global downregulation of DLK1-DIO3-derived miRNAs in thyroid cancer. These insights offer valuable contributions to the field of thyroid carcinoma research (AU) | |
| FAPESP's process: | 17/21660-0 - Functional characterization of microRNA-495-3P in Thyroid Cancer |
| Grantee: | Letícia Ferreira Alves |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |