Novel circulating microRNA signature in chronic Chagas disease

SR VILLAR; ALFONSO HERREROS-CABELLO; FRANCISCO CALLEJAS-HERNÁNDEZ; MARÍA C. MAZA; JAVIER DEL MORAL-SALMORAL; MARIO GÓMEZ-MONTES; HÉCTOR O.RODRÍGUEZ-ANGULO; IRENE CARRILLO; MIGUEL GÓRGOLAS; PAU BOSCH-NICOLAU; ISRAEL MOLINA; JOSÉ A. PÉREZ-MOLINA; BEGOÑA MONGE-MAILLO; OSCAR A. BOTTASSO; JUAN BELOSCAR; ANA ROSA PEREZ; MANUEL FRESNO; NURIA GIRONÉS

Scientific reports

Nature Publishing Group

Año: 2024

2045-2322

Chagas disease affects about 7 million people worldwide. It is endemic in Latin America, and because of migration, is also present in non-endemic regions of the world. Twenty to thirty percent of chronically infected patients develop chronic Chagas cardiomyopathy after decades from acute infection. Identifying biomarkers of heart disease progression is necessary to develop better therapeutic and preventive strategies. microRNAs are small RNAs that regulate gene expression and are increasingly found as reliable biomarkers of disease. To identify new circulating miRNAs with levels specifically altered in Chagasic patients that could serve as biomarkers and/or potential therapeutic targets, we performed an exploratory small RNA sequencing from the plasma of patients. Then, we performed de novo microRNA prediction and identified 4 potential new microRNAs. Two of them were validated by quantitative reverse transcription PCR after the analysis of samples from patients with chronic Chagas disease and samples from healthy controls. The results showed that the levels of the temporarily named miR-Contig-1519 and miR-Contig-3244 were lower in indeterminate and mild and moderate chronic Chagas cardiomyopathy patients than in healthy controls. After that, we also studied the levels of other known circulating microRNAs described as biomarkers in non-Chagasic cardiomyopathies. We observed lower levels of miR-148a-3p and higher levels of miR-224-5p in indeterminate, mild and moderate chronic Chagas cardiomyopathy patients compared to healthy controls. Thus, although more studies are needed, we have described a specific circulating microRNA signature defined by low miR-Contig-3244, miR-Contig-1519 and miR-148a-3p, and high miR-224-5p levels for patients with Chronic Chagas disease. Finally, we predicted in silico that these altered circulating microRNAs could affect the expression of target genes involved in different cellular pathways and biological processes, which should be explored in the future.