Architha Tca, Juanitaa George Raj, Vijayalalitha Ramanarayanan, Jayasuriya Ravichandran, Athira Gopinathan, Balamurugan Ramachandran, Ganesan Kumar, Ramkumar Kunka Mohanram
Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Chengalpattu Dt., Tamil Nadu, India.
SRM Medical Hospital and Research Centre, SRM Institute of Science and Technology, Kattankulathur 603 203, Chengalpattu Dt., Tamil Nadu, India.
Cells. 2024 Mar 5;13(5):456. doi: 10.3390/cells13050456.
Non-healing lesions in diabetic foot ulcers are a significant effect of poor angiogenesis. Epigenetic regulators, mainly lncRNA and miRNA, are recognized for their important roles in disease progression. We deciphered the regulation of lncRNA NEAT1 through the miR-146a-5p/mafG axis in the progression of DFU. A lowered expression of lncRNA NEAT1 was associated with dysregulated angiogenesis through the reduced expression of , , and in chronic ulcer subjects compared to acute DFU. This was validated by silencing NEAT1 by SiRNA in the endothelial cells which resulted in the transcriptional repression of target genes. Our in silico analysis identified miR-146a-5p as a potential target of lncRNA NEAT1. Further, silencing NEAT1 led to an increase in the levels of miR-146a-5p in chronic DFU subjects. This research presents the role of the lncRNA NEAT1/miR-146a-5p/mafG axis in enhancing angiogenesis in DFU.
糖尿病足溃疡中的不愈合创面是血管生成不良的一个显著后果。表观遗传调控因子，主要是长链非编码RNA（lncRNA）和微小RNA（miRNA），因其在疾病进展中的重要作用而被认可。我们解析了lncRNA NEAT1通过miR-146a-5p/mafG轴在糖尿病足溃疡进展中的调控作用。与急性糖尿病足溃疡相比，慢性溃疡患者中lncRNA NEAT1表达降低与血管生成失调有关，其机制是通过降低 、 和 的表达。这一结果在内皮细胞中通过小干扰RNA（SiRNA）沉默NEAT1得到验证，其导致了靶基因的转录抑制。我们的计算机分析确定miR-146a-5p是lncRNA NEAT1的一个潜在靶点。此外，沉默NEAT1导致慢性糖尿病足溃疡患者中miR-146a-5p水平升高。本研究揭示了lncRNA NEAT1/miR-146a-5p/mafG轴在增强糖尿病足溃疡血管生成中的作用。
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