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基于生物信息学方法评价 miRNAs 对实验模型中 T2DM 胰岛素抵抗的 BDNF 和 IGF1 基因的调控。

Evaluation of miRNAs regulation of BDNF and IGF1 genes in T2DM insulin resistance in experimental models: bioinformatics based approach.

机构信息

Universidade Estadual do Ceará - UECE, Instituto Superior de Ciências Biomédicas - ISCB, Laboratório de Bioquímica e Expressão Gênica - LABIEX, Programa de Pós-graduação em Biotecnologia - RENORBIO, Fortaleza, CE, Brasil.

Centro de Hematologia e Hemoterapia do Ceará - HEMOCE, Departamento de Ensino e Pesquisa, Fortaleza, CE, Brasil.

出版信息

Braz J Biol. 2022 May 4;84:e256691. doi: 10.1590/1519-6984.256691. eCollection 2022.

DOI:10.1590/1519-6984.256691
PMID:35544787
Abstract

microRNAs (miRNAs) are recognized as diabetes mellitus type 2 (T2DM) biomarkers useful for disease metabolism comprehension and have great potential as therapeutics targets. BDNF and IGF1 increased expression are highly involved in the benefits of insulin and glucose paths, however, they are down-regulated in insulin resistance conditions, while their expression increase is correlated to the improvement of glucose and insulin metabolism. Studies suggest the microRNA regulation of these genes in several different contexts, providing a novel investigation approach for comprehending T2DM metabolism and revealing potential therapeutic targets. In the present study, we investigate in different animal models (human, rat, and mouse) miRNAs that target BDNF and IGF1 in skeletal muscle tissue with T2DM physiological conditions. Bioinformatics tools and databases were used to miRNA prediction, molecular homology, experimental validation of interactions, expression in the studied physiological condition, and network interaction. The findings showed three miRNAs candidates for IGF1(miR-29a, miR-29b, and miR-29c) and one for BDNF (miR-206). The experimental evaluations and the search for the expression in skeletal muscle from T2DM subjects confirmed the predicted interaction between miRNA-mRNA for miR-29b and miR-206 through human, rat, and mouse models. This interaction was reaffirmed in multiple network analyses. In conclusion, our results show the regulation relationship between miR-29b and miR-206 with the investigated genes, in several tissues, suggesting an inhibition pattern. Nevertheless, these data show a large number of possible interaction physiological processes, for future biotechnological prospects.

摘要

微小 RNA(miRNAs)被认为是 2 型糖尿病(T2DM)的生物标志物,有助于理解疾病代谢,并具有作为治疗靶点的巨大潜力。BDNF 和 IGF1 的表达增加高度参与胰岛素和葡萄糖途径的益处,但在胰岛素抵抗条件下它们被下调,而它们的表达增加与葡萄糖和胰岛素代谢的改善相关。研究表明,这些基因的 microRNA 调节在几种不同的情况下提供了一种新的研究方法,用于理解 T2DM 代谢并揭示潜在的治疗靶点。在本研究中,我们在不同的动物模型(人类、大鼠和小鼠)中研究了骨骼肌组织中针对 T2DM 生理条件下的 BDNF 和 IGF1 的 miRNA。生物信息学工具和数据库用于 miRNA 预测、分子同源性、相互作用的实验验证、研究生理条件下的表达以及网络相互作用。研究结果显示了三个候选 IGF1 (miR-29a、miR-29b 和 miR-29c)和一个候选 BDNF(miR-206)的 miRNA。通过人类、大鼠和小鼠模型对实验评估和 T2DM 患者骨骼肌中的表达进行搜索,证实了 miR-29b 和 miR-206 与 miRNA-mRNA 之间的预测相互作用。通过多个网络分析再次证实了这种相互作用。总之,我们的结果显示了 miR-29b 和 miR-206 与研究基因之间的调节关系,在几种组织中表明存在抑制模式。然而,这些数据显示了大量可能的相互作用生理过程,为未来的生物技术前景提供了参考。

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