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环状RNA Dock6通过调控小鼠微小RNA-let-7g-5p/胰岛素样生长因子1受体,驱动小鼠和小鼠肝细胞中与代谢功能障碍相关的脂肪性肝病进展。

CircDock6 drives metabolic dysfunction-associated steatotic liver disease progression in mice and mouse hepatocytes via mmu-let-7g-5p/insulin-like growth factor 1 receptor regulation.

作者信息

Lu Hongpeng, Ding Xiaoyun, Li Peifei

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, China.

出版信息

J Int Med Res. 2025 Aug;53(8):3000605251362984. doi: 10.1177/03000605251362984. Epub 2025 Aug 12.

Abstract

ObjectiveCircular RNAs belong to a category of noncoding RNAs that feature a unique continuous, covalently bonded ring configuration. Recent research indicates that circular RNAs are essential for the development of metabolic dysfunction-associated steatotic liver disease. This study sought to examine the functional role and molecular mechanism of circDock6 in metabolic dysfunction-associated steatotic liver disease.MethodsQuantitative reverse transcription polymerase chain reaction was performed to determine expression patterns in liver tissues from high-fat diet- and standard diet-fed mice in vivo. Triglyceride detection, western blot analysis, and oil red O staining were performed to evaluate the regulatory effect of circDock6 on metabolic dysfunction-associated steatotic liver disease in vitro.Results was found to be markedly overexpressed in high-fat diet liver tissues compared with that in standard diet tissues. Moreover, knockdown of expression lowered triglyceride content and lipid droplet formation. Mechanistically, circDock6 acted as a molecular sponge for mmu-let-7g-5p, which regulated insulin-like growth factor 1 receptor expression and contributed to the progression of metabolic dysfunction-associated steatotic liver disease. knockdown suppressed metabolic dysfunction-associated steatotic liver disease progression by modulating insulin-like growth factor 1 receptor via mmu-let-7g-5p targeting.ConclusionOur study identified circDock6 as a novel regulator of metabolic dysfunction-associated steatotic liver disease pathogenesis through the mmu-let-7g-5p/insulin-like growth factor 1 receptor axis, indicating its potential as a therapeutic target for metabolic dysfunction-associated steatotic liver disease intervention.

摘要

目的

环状RNA属于一类非编码RNA,其具有独特的连续共价键环结构。近期研究表明,环状RNA对于代谢功能障碍相关脂肪性肝病的发展至关重要。本研究旨在探讨circDock6在代谢功能障碍相关脂肪性肝病中的功能作用及分子机制。

方法

采用定量逆转录聚合酶链反应来确定高脂饮食喂养和标准饮食喂养小鼠肝脏组织中的表达模式。进行甘油三酯检测、蛋白质印迹分析和油红O染色,以评估circDock6在体外对代谢功能障碍相关脂肪性肝病的调节作用。

结果

与标准饮食组织相比,circDock6在高脂饮食肝脏组织中明显过表达。此外,circDock6表达的敲低降低了甘油三酯含量和脂滴形成。机制上,circDock6作为mmu-let-7g-5p的分子海绵,调节胰岛素样生长因子1受体的表达,并促进代谢功能障碍相关脂肪性肝病的进展。circDock6敲低通过靶向mmu-let-7g-5p调节胰岛素样生长因子1受体,从而抑制代谢功能障碍相关脂肪性肝病的进展。

结论

我们的研究通过mmu-let-7g-5p/胰岛素样生长因子1受体轴,将circDock6鉴定为代谢功能障碍相关脂肪性肝病发病机制的新型调节因子,表明其作为代谢功能障碍相关脂肪性肝病干预治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bea/12344330/3dfacd14d9a0/10.1177_03000605251362984-fig1.jpg

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