Department of Pathology and Laboratory Medicine, University of Western Ontario, London, Ontario, Canada.
PLoS One. 2024 Jul 23;19(7):e0302772. doi: 10.1371/journal.pone.0302772. eCollection 2024.
Noncoding RNAs play a part in many chronic diseases and interact with each other to regulate gene expression. MicroRNA-9-5p (miR9) has been thought to be a potential inhibitor of diabetic cardiomyopathy. Here we examined the role of miR9 in regulating cardiac fibrosis in the context of diabetic cardiomyopathy. We further expanded our studies through investigation of a regulatory circularRNA, circRNA_012164, on the action of miR9. We showed at both the in vivo and in vitro level that glucose induced downregulation of miR9 and upregulation of circRNA_012164 resulted in the subsequent upregulation of downstream fibrotic genes. Further, knockdown of circRNA_012164 shows protective effects in cardiac endothelial cells and reverses increased transcription of genes associated with fibrosis and fibroblast proliferation through a regulatory axis with miR9. This study presents a novel regulatory axis involving noncoding RNA that is evidently important in the development of cardiac fibrosis in diabetic cardiomyopathy.
非编码 RNA 在许多慢性疾病中发挥作用，并相互作用以调节基因表达。MicroRNA-9-5p (miR9) 被认为是糖尿病心肌病的潜在抑制剂。在这里，我们研究了 miR9 在调节糖尿病心肌病中心脏纤维化中的作用。我们通过研究 circRNA_012164 对 miR9 作用的调控，进一步扩展了我们的研究。我们在体内和体外水平均表明，葡萄糖诱导的 miR9 下调和 circRNA_012164 的上调导致下游纤维化基因的随后上调。此外，circRNA_012164 的敲低在心脏内皮细胞中显示出保护作用，并通过与 miR9 相关的调节轴逆转与纤维化和成纤维细胞增殖相关基因的转录增加。这项研究提出了一个涉及非编码 RNA 的新调节轴，在糖尿病心肌病中心脏纤维化的发展中显然很重要。
