Banca de QUALIFICAÇÃO: THIAGO JESUS DA SILVA XAVIER

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : THIAGO JESUS DA SILVA XAVIER
DATE: 09/09/2025
TIME: 09:00
LOCAL: Videoconferência
TITLE:

Análise do papel das funções de APE1/Ref-1 na regulação transcricional de ELK1 e seus genes-alvo durante estimulação inflamatória e estresse oxidativo em diferentes linhagens celulares

KEY WORDS:

APE1. DNA repair. Inflammation. Transcriptional regulation. ELK1.

PAGES: 23
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

APE1/Ref-1 is a multifunctional mammalian protein that plays a role in several cellular processes. Its main functions are: endonuclease activity in the base excision repair (BER) pathway, exerted by the C-terminal portion of the protein; and redox activity, which plays a key role in combating oxidative stress, making it an important protein for cellular homeostasis and maintaining genomic stability. Furthermore, both redox and repair functions play a role in the transcriptional regulation of genes related to inflammatory processes, cell division, RNA metabolism, and other pathways. Therefore, further research is needed to better elucidate the genes and transcription factors targeted by each APE1 function and their phenotypic consequences. In this context, in previous work, our research group analyzed the transcriptome of U937 monocytes stimulated by lipopolysaccharide and treated separately with the inhibitors E3330 and MX. It was observed that genes potentially targeted by the transcription factor ELK1 were downregulated after both treatments, with ELK1 being the transcription factor most enriched for genes downregulated after E3330 treatment. Furthermore, ELK1 mRNA expression was decreased in both treatments. Taking these data as a starting point, the present study sought to precisely analyze the relationship between APE1 functions and the regulation of ELK1 expression and its targets. Western blotting and RT-qPCR experiments were performed to quantify the expression of ELK1 and its targets in extracts from U937 cells treated with MX and E3330. Both ELK1 and its target genes were significantly altered after treatment, both at the transcriptional and protein levels. The data presented here suggest that both functions of APE1 significantly affect ELK1 expression and interfere with the regulation of its targets. Finally, this work indicates ELK1 as a new target of APE1 functions, which needs to be further investigated.

COMMITTEE MEMBERS:
Interno - 1149356 - ELIZEU ANTUNES DOS SANTOS
Interno - 2195251 - HUGO ALEXANDRE DE OLIVEIRA ROCHA
Presidente - 1453487 - KATIA CASTANHO SCORTECCI