Laboratory of Human and Medical Genetics, Graduate Program in Genetics and Molecular Biology, Federal University of Para, Belem, PA, Brazil.
Instituto Tecnológico Vale Desenvolvimento Sustentável Vale, Institute of Technology, Belem, PA, Brazil.
Front Endocrinol (Lausanne). 2022 Nov 24;13:1033809. doi: 10.3389/fendo.2022.1033809. eCollection 2022.
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.
We analyzed samples of T1DM patients and control individuals (normal glucose tolerance) by high throughput miRNA sequencing (miRNome). Next, five miRNAs - , , , and 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.
Overall, 41 miRNAs were differentially expressed in T1DM patients compared to control. 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, showed AUC>0.85, being suggested as potential biomarker to T1DM.
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. and were highlighted in our results, possibly acting on nuclear and mitochondrial dysfunction and, subsequently, T1DM dysregulation.
鉴于 miRNA 作为生物标志物的潜在作用及其与核基因和线粒体基因的相互作用，我们研究了 1 型糖尿病 (T1DM) 患者的 miRNA 表达谱，包括考虑核和线粒体功能的它们所涉及的途径。
我们通过高通量 miRNA 测序 (miRNome) 分析了 T1DM 患者和对照个体（正常糖耐量）的样本。接下来，通过 RT-qPCR 验证了五个 miRNA - 、 、 、 和 。miRTarBase 和 mitoXplorer 数据库提取了靶基因的鉴定。我们还进行了接收器操作特征 (ROC) 曲线分析，AUC>0.85 的 miRNA 被认为是潜在的生物标志物。
总体而言，与对照组相比，T1DM 患者有 41 个 miRNA 表达差异。 具有最多的预测靶基因，与包括胰岛素信号和凋亡在内的多个途径相关。41 个差异表达 miRNA 中有 34.1%（14/41）也靶向线粒体基因，其中 80.5%（33/41）靶向参与线粒体代谢的核基因。所有验证的五个 miRNA 在 T1DM 中均上调。其中， 表现出 AUC>0.85，被建议作为 T1DM 的潜在生物标志物。
我们的研究结果表明，41 个差异表达的 miRNA 能够准确区分 T1DM 和对照组。此外，我们还证明了这些 miRNA 对包括线粒体代谢在内的许多代谢途径的影响。 和 在我们的研究结果中得到了强调，它们可能作用于核和线粒体功能障碍，进而导致 T1DM 失调。
