van Zonneveld Anton Jan, Kölling Malte, Bijkerk Roel, Lorenzen Johan M
Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Division of Nephrology, University Hospital Zürich, Zürich, Switzerland.
Nat Rev Nephrol. 2021 Dec;17(12):814-826. doi: 10.1038/s41581-021-00465-9. Epub 2021 Aug 11.
Circular RNAs (circRNAs) are a class of endogenously expressed regulatory RNAs with a single-stranded circular structure. They are generated by back splicing and their expression can be tightly regulated by RNA binding proteins. Cytoplasmic circRNAs can function as molecular sponges that inhibit microRNA-target interactions and protein function or as templates for the efficient generation of peptides via rolling circle amplification. They can also act as molecular scaffolds that enhance the reaction kinetics of enzyme-substrate interactions. In the nucleus, circRNAs might facilitate chromatin modifications and promote gene expression. CircRNAs are resistant to degradation and can be packaged in extracellular vesicles and transported in the circulation. Initial studies suggest that circRNAs have roles in kidney disease and associated cardiovascular complications. They have been implicated in hypertensive nephropathy, diabetic kidney disease, glomerular disease, acute kidney injury and kidney allograft rejection, as well as in microvascular and macrovascular complications of chronic kidney disease, including atherosclerotic vascular disease. In addition, several circRNAs have been reported to have oncogenic or tumour suppressor roles or to regulate drug resistance in kidney cancer. The available data suggest that circRNAs could be promising diagnostic and/or prognostic biomarkers and potential therapeutic targets for kidney disease, cardiovascular disease and kidney cancer.
环状RNA(circRNAs)是一类内源性表达的具有单链环状结构的调控RNA。它们通过反向剪接产生,其表达可受到RNA结合蛋白的严格调控。细胞质circRNAs可作为分子海绵抑制微小RNA-靶标相互作用和蛋白质功能,或作为通过滚环扩增高效生成肽的模板。它们还可作为分子支架增强酶-底物相互作用的反应动力学。在细胞核中,circRNAs可能促进染色质修饰并促进基因表达。circRNAs对降解具有抗性,可被包裹在细胞外囊泡中并在循环中运输。初步研究表明,circRNAs在肾脏疾病及相关心血管并发症中发挥作用。它们与高血压肾病、糖尿病肾病、肾小球疾病、急性肾损伤和肾移植排斥反应有关,也与慢性肾病的微血管和大血管并发症有关,包括动脉粥样硬化性血管疾病。此外,据报道,几种circRNAs在肾癌中具有致癌或抑癌作用或调节耐药性。现有数据表明,circRNAs有望成为肾脏疾病、心血管疾病和肾癌的诊断和/或预后生物标志物以及潜在的治疗靶点。