PRESENCE OF NUCLEAR MUTATIONS IN COMPLEX IV OF OXIDATIVE PHOSPHORYLATION IN BREAST CANCER

PRESENCE OF NUCLEAR MUTATIONS IN COMPLEX IV OF OXIDATIVE PHOSPHORYLATION IN BREAST CANCER

• Autor
• Ricardo Cunha de Oliveira
• Co-autores
• Giovanna Chaves Cavalcante
• Resumo

• Introduction: Breast cancer (BC) is considered a public health problem that has been increasingly debated in recent years. This is due to the fact that it has one of the highest numbers in relation to its incidence and mortality among the various types of cancer. From this, the discovery of perspectives that can help in the treatment, diagnosis and prognosis of people with BC has been carried out, mainly by investigating knowledge that are not well elucidated yet, such as the mitochondrial relationship of oxidative phosphorylation (OXPHOS), performed in mitochondria, and this type of cancer. Mitochondria are organelles present in eukaryotic organisms that have several functions, among these are the production of cellular energy through OXPHOS, a reaction in which there is the formation of several reactive oxygen species (ROS). Thus, for an adequate mitochondrial homeostasis, Complex IV (COX) ends up being one of the main reducers and agents in the mitochondrial electrolyte balance. Objective: To investigate the presence of nuclear alterations in Complex IV of OXPHOS in breast cancer. Methodology: An in silico approach was carried out, through the cBioPortal platform, in three public BC databases (DBs), totaling 1,601 patients. For the analysis, Microsoft Excel software was used to tabulate genetic alterations, which focused on the search for single nucleotide polymorphisms (SNPs) and Deletions/Insertions (INDELs). Subsequently, there was a search for whether such alterations were reported in the literature and the physiological function of the altered genes through the National Center for Biotechnology Information (NCBI) and Gene Ontology (GO). To select the Complex IV genes to be investigated, the MitoXplorer platform was used. Results: A total of 42 mutations  were identified in all 18 screened genes. The COX5B was the only gene with alterations in all BDs and with the highest number of mutations (five) together with COX7A2L  and COX7B2. Two mutations of interest (missense) were found in COX5B, but these have not been reported in the literature. It is worth noting that, in BC, COX5B overexpression has been associated with low survival and high cytokine production (angiogenic condition), so that the loss of its function can lead to increased ROS production, loss of energy production and cellular senescence, leading to cell death. Regarding COX7A2L, it has also been shown to be overexpressed in BC and to promote tumor growth. The alterations found in this gene are not yet elucidated, and four of the mutations observed here were missense, while one was nonsense. In addition, no literature on the association of the COX7B2 gene with BC was found. Conclusion: This study suggests COX5B, COX7A2L and COX7B2 genes as possible biomarkers, which can be linked to treatment, diagnosis and prognosis in BC. Notably, this is the first work that demonstrates mutations in COX7B2 in patients with BC, thus indicating that the mitochondrial relationship of OXPHOS with this type of cancer may be closely related and not so well characterized.

• Palavras-chave
• Breast Carcinoma, Cell Death, Mitochondria, Oxidative Phosphorylation, Homeostasis
• Área Temática
• Graduação