Freitas Raquel, Felipe Stela, Pacheco Christina, Faria Emmanuelle, Martins Jonathan, Fortes Jefferson, Silva Denner, Oliveira Paulo, Ceccatto Vania
Laboratory of Biochemistry and Molecular Biology of UECE-LABIEX, Superior Institute of Biomedical Science-ISCB, State University of Ceará-UECE, Silas Munguba Avenue, 1700, Fortaleza 60714-903, CE, Brazil.
Departamento de Biologia Celular e Molecular, Federal University of Paraíba-UFPB, João Pessoa 58051-900, PB, Brazil.
Biomedicines. 2025 May 14;13(5):1192. doi: 10.3390/biomedicines13051192.
: MicroRNAs (miRNAs) are molecules involved in biological regulation processes, including type 2 diabetes and its complications development. Single nucleotide polymorphisms (SNPs) can alter miRNA mechanisms, resulting in loss or gain effects. VEGFA is recognized for its role in angiogenesis. However, its overexpression can lead to deleterious effects, such as disorganized and inefficient vasculature. Under hyperglycemic conditions, VEGFA expression seems to increase, which may contribute to the development of microvascular and macrovascular diabetic complications. Several miRNAs are associated with VEGFA regulation and seem to act in the prevention of dysregulated expression. This study aimed to investigate SNPs in miRNA regions related to the loss effect in VEGFA regulation, examining their frequency and potential physiological effects in the development of diabetic complications. : VEGFA-targeting miRNAs were identified using the R package multimiR, with validated and predicted results. Tissue expression analysis and SNP search were data-mined with Python 3 for miRNASNP-v3 SNP raw databases. Allele frequencies were obtained from dbSNP. The miRNA-mRNA interaction comparison was obtained in the miRmap tool through Python 3. MalaCards were used to infer physiological disease association. : The variant rs371699284 was selected in hsa-miR-654-3p among 103 potential VEGFA-targeting miRNAs. This selected SNP demonstrated promising results in bioinformatics predictions, tissue-specific expression, and population frequency, highlighting its potential role in miRNA regulation and the resulting loss in VEGFA-silencing efficiency. : Our findings suggest that carriers of rs1238947970 may increase susceptibility to diabetic microvascular and macrovascular complications. Furthermore, in vitro and in silico studies are necessary to better understand these processes.
微小RNA（miRNA）是参与生物调节过程的分子，包括2型糖尿病及其并发症的发展。单核苷酸多态性（SNP）可改变miRNA机制，导致功能丧失或获得效应。血管内皮生长因子A（VEGFA）因其在血管生成中的作用而被认可。然而，其过度表达可导致有害影响，如血管系统紊乱和效率低下。在高血糖条件下，VEGFA表达似乎增加，这可能有助于糖尿病微血管和大血管并发症的发展。几种miRNA与VEGFA调节相关，似乎在预防表达失调中起作用。本研究旨在调查与VEGFA调节功能丧失效应相关的miRNA区域中的SNP，检查它们在糖尿病并发症发展中的频率和潜在生理效应。：使用R包multimiR鉴定靶向VEGFA的miRNA，结果经过验证和预测。使用Python 3对miRNASNP-v3 SNP原始数据库进行数据挖掘，进行组织表达分析和SNP搜索。等位基因频率从dbSNP获得。通过Python 3在miRmap工具中进行miRNA- mRNA相互作用比较。使用MalaCards推断生理疾病关联。：在103种潜在的靶向VEGFA的miRNA中，选择了hsa-miR-654-3p中的rs371699284变体。该选定的SNP在生物信息学预测、组织特异性表达和群体频率方面显示出有前景的结果，突出了其在miRNA调节中的潜在作用以及VEGFA沉默效率的降低。：我们的研究结果表明，rs1238947970携带者可能增加患糖尿病微血管和大血管并发症的易感性。此外，需要进行体外和计算机模拟研究以更好地理解这些过程。
