Análise de DNA circular extracromossômico em células somáticas

• Ano de defesa: 2024
• Autor(a) principal: Paulino, Mary Audeny Torres
• Orientador(a): Pogue, Robert
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Católica de Brasília
• Programa de Pós-Graduação: Programa Stricto Sensu em Ciências Genômicas e Biotecnologia
• Departamento: Escola de Saúde e Medicina
• País: Brasil
• Palavras-chave em Português: EccDNA; Bioinformática; Genoma
• Palavras-chave em Inglês: EccDNA; Bioinformatics; Genome
• Área do conhecimento CNPq: CNPQ::CIENCIAS DA SAUDE
• Link de acesso: https://bdtd.ucb.br:8443/jspui/handle/tede/3540

Circular extrachromosomal DNA (eccDNA) is a type of double-stranded circular DNA that originates from chromosomes and is found in normal and cancerous cells. Understanding eccDNA diversity in normal somatic cells provides information to elucidate the mechanisms underlying its development and genome stability. This study conducts a bioinformatic analysis of eccDNAs obtained from different human fibroblast (hFib) lines from three donors (D1, D2 and D3). We observed that the number of eccDNAs varies between donors, without a clear pattern regarding genomic distribution. Approximately 50% of eccDNAs were derived from coding regions, followed by regulatory regions (30.94%) with a predominance of enhancers, which represented approximately 50% of all regulatory elements identified. Donor three presented the largest quantity of eccDNAs, showing a greater diversity of regulatory elements, including the presence of eccDNAs that combine multiple regulatory elements. Enrichment analysis of genes associated with eccDNAs revealed their relationship with metabolic processes, growth regulation and cell survival. Signaling pathways, such as the epidermal growth factor receptor (EGFR) and the ErbB pathway, were significantly enriched, as was the Rap1 signaling pathway, which regulates cell adhesion, migration and polarity. It was statistically observed that eccDNAs tend to be mapped in regions lacking CpG islands, in addition to being more commonly associated with euchromatin regions, demonstrating a connection with the findings that demonstrated that genes in eccDNAs participate in DNA replication processes. Furthermore, the high presence of LINEs and SINEs elements suggests a possible role in the formation of eccDNAs. Our findings reveal that the characteristics of eccDNA and the functions of eccDNA genes are associated with the cell type of origin, in addition to indicating that eccDNAs can originate from both chromatin regions, but additional studies are needed to deepen the understanding of this relationship.