PPARs no câncer de fígado: sintenia e interações aplicados a medicina evolutiva

Abstract

Liver cancer is the sixth most common diagnosis and the third cause of death. Peroxisome proliferator-activated nuclear receptors (PPARs) are a group of genes that act as transcription factors and have recently been indicated as potential therapeutics for liver cancer. Thus, we studied the PPARs genes associated with their interactions and synteny in an evolutionary medicine approach to liver cancer. The selection of the PPAR family and the primary analysis of their functions were obtained on the NCBI and UniProt platforms. The search for gene interactions was carried out using the protein association network in the STRING database, for the PPAR, PPAR and PPAR subtypes and the synteny analysis of this gene group was carried out. The return of information indicated that the set of genes and gene products evaluated have multiple functionalities of varying magnitude and complexity, being related to liver metabolism and its risk factors or not with liver cancer. In addition to being Mendelian units, they also mainly present positive and negative pleiotropic effects, directly or indirectly involved with liver diseases or healthy phenotypes, such as activities related to thyroid function, spermatogenesis, bone formation and differentiation, satiety control, circadian cycle, among others. These analyzes that are just beginning show promise for an early prognosis involving not only the molecular interactions of PPARs, but their positions in the genome. In this sense, genes are also modulated sometimes to develop their tumorigenic expression, sometimes not, suggesting that their study focused mainly on a healthy phenotype can facilitate preventive actions. This basic approach to evolutionary medicine identified new biomarker targets for hepatocellular carcinoma that could be effectively useful for future genetic evaluations, aiming to better prevent diseases and promote health.