Global miRNA expression reveals novel nuclear and mitochondrial interactions in Type 1 diabetes mellitus.
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Ferraz Rafaella Sousa, Santos Lucas Cauê Bezerra, da-Silva-Cruz Rebecca Lais, Braga-da-Silva Cintia Helena, Magalhães Leandro, Ribeiro-Dos-Santos Arthur, Vidal Amanda, Vinasco-Sandoval Tatiana, Reis-das-Mercês Laís, Sena-Dos-Santos Camille, Pereira Adenilson Leão, Silva Lilian Souza D'Albuquerque, de Melo Franciane T Cunha, de Souza Ana Carolina C Braga, Leal Valéria S Galvão, de Figueiredo Priscila B Barbosa, Neto João F Abrahão, de Moraes Lorena Vilhena, de Lemos Gabriela Nascimento, de Queiroz Natércia Neves Marques, Felício Karem Miléo, Cavalcante Giovanna C, Ribeiro-Dos-Santos Ândrea, Felício João Soares
Аннотация
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.