ABSTRACT
Breast cancer (BC) is the type of neoplasm that most affects women worldwide. It is known that one of the hallmarks of cancer is the resistance to cell death with the evasion of apoptosis. Considering the relevance of TP53, BCL2, CASP3, and CASP9 genes for the occurrence of the intrinsic apoptosis, this study investigated the distribution of the genetic variants rs17880560 (TP53), rs11269260 (BCL2), rs4647655 (CASP3), rs4645982, and rs61079693 (CASP9), as well as genetic ancestry and clinical data, in a BC cohort from the Brazilian Amazon that other variants in these genes might play a role in this process. In the present study, 22 breast cancer tissues and 10 non-cancerous tissues were used, therefore, 32 samples from different patients were subjected to genotyping. We observed that breastfeeding and cancer history were factors that need to be considered for BC (p = 0.022). Therefore, this study contributed to a greater understanding of intrinsic apoptosis in BC, reinforcing previous data that suggest that the history of cancer might be a condition that affects the development of BC and that breastfeeding may act as a protective factor for this type of cancer. We recommend more studies on the genetic factors investigated here, aiming at a future with tools that can help in the early diagnosis.
ABSTRACT
Background: Considering the potential role of miRNAs as biomarkers and their interaction with both nuclear and mitochondrial genes, we investigated the miRNA expression profile in type 1 diabetes (T1DM) patients, including the pathways in which they are involved considering both nuclear and mitochondrial functions. Methods: We analyzed samples of T1DM patients and control individuals (normal glucose tolerance) by high throughput miRNA sequencing (miRNome). Next, five miRNAs - hsa-miR-26b-5p, hsa-let-7i-5p, hsa-miR-143-3p, hsa-miR-501-3p and hsa-miR-100-5p - were validated by RT-qPCR. The identification of target genes was extracted from miRTarBase and mitoXplorer database. We also performed receiver operating characteristic (ROC) curves and miRNAs that had an AUC > 0.85 were considered potential biomarkers. Results: Overall, 41 miRNAs were differentially expressed in T1DM patients compared to control. Hsa-miR-21-5p had the highest number of predicted target genes and was associated with several pathways, including insulin signaling and apoptosis. 34.1% (14/41) of the differentially expressed miRNAs also targeted mitochondrial genes, and 80.5% (33/41) of them targeted nuclear genes involved in the mitochondrial metabolism. All five validated miRNAs were upregulated in T1DM. Among them, hsa-miR-26b-5p showed AUC>0.85, being suggested as potential biomarker to T1DM. Conclusion: Our results demonstrated 41 DE miRNAs that had a great accuracy in discriminating T1DM and control group. Furthermore, we demonstrate the influence of these miRNAs on numerous metabolic pathways, including mitochondrial metabolism. Hsa-miR-26b-5p and hsa-miR-21-5p were highlighted in our results, possibly acting on nuclear and mitochondrial dysfunction and, subsequently, T1DM dysregulation.
