Efeitos da leptina sobre a regulação de componentes do sistema ubiquitina proteassoma em células de carcinoma epiderrmoide de boca

Abstract

Leptin, a hormone that regulates energy balance and body weight control, may be involved in the etiopathogenesis and progression of different types of cancer. In oral squamous cell carcinoma, the leptin signaling pathway was associated with changes in the neoplastic phenotype and increased expression of genes related to cell proliferation, invasion and angiogenesis. In addition to the leptin signaling pathway, the ubiquitin-proteasome system, responsible for the proteolytic degradation switch, has aroused interest for investigation in the field of oral carcinogenesis. These two targets were adopted as the focus of the study, since both are involved in feelings of emotions and changes in the cell cycle. Thus, this study aimed to investigate whether leptin modulates the gene expression of components of the ubiquitin proteasome system and the behavior of oral squamous cell carcinoma cells. The bioinformatics tools String Database and MetaCore Bioinformatics software was used to test the hypothesis that leptin interacts with ubiquitin-proteasome system components, aiming to conduct the in vitro assays. The oral cancer cell lines, SCC4 and SCC9, were treated with recombinant leptin and the expression levels of genes of the ubiquitin-proteasome system were quantified by qRT-PCR, including USP2, UBA, UBC, PSMD4 and PSME3. Cell viability and cell cycle assays were performed. USP2 was silenced by the siRNA sequence in leptin-treated cells and the proliferative profile was verified. The in silico analysis revealed an interaction network between leptin and components of the ubiquitin-proteasome system. Leptin favored cell proliferation, according to increased mRNA expression of the USP2 oncogene and cell cycle regulatory genes, UBA and UBC. The proliferative effect promoted by leptin was impaired when USP2 was silenced by siRNA, suggesting a link between leptin and the UPS2 oncogene. The results showed that leptin can modulate gene expression of the ubiquitin-proteasome system, suggesting this association as an important factor modifying the neoplastic behavior of oral cancer cells, and as a potential therapeutic target.