The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, PR China.
The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, PR China; Clinical Laboratory, China Japan Friendship Hospital, PR China.
Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Aug;1865(8):158727. doi: 10.1016/j.bbalip.2020.158727. Epub 2020 Apr 27.
The current study aims to evaluate whether peripheral blood miR-324-5p could be used to differentiate patients with metabolic disorders and healthy controls. Our data showed that miR-324-5p levels were elevated in the peripheral blood of patients with hyperglycemia or hyperlipidemia. In addition, the expression of miR-324-5p was enhanced in the peripheral blood and liver of db/db mice. Further study indicated that overexpression of miR-324-5p reduced the activation of the AKT/GSK pathway and increased lipid accumulation, while the inhibition of miR-324-5p activated the AKT/GSK pathway and decreased lipid accumulation. A dual luciferase assay revealed that Rho-associated coiled-coil containing protein kinase 1 (ROCK1) was a target gene of miR-324-5p. In addition, silencing ROCK1 deteriorated lipid and glucose metabolism. More importantly, knockdown of ROCK1 reversed the miR-324-5p inhibitor-induced improvement of glucose and lipid metabolism. In summary, miR-324-5p plays a regulatory role in glucose and lipid metabolism by targeting ROCK1, which is involved in metabolic disorders. The use of miR-324-5p in diagnosing metabolic syndrome is worth investigating and may benefit patients.
本研究旨在评估外周血 miR-324-5p 是否可用于区分代谢紊乱患者和健康对照者。我们的数据显示,高血糖或高血脂患者外周血中 miR-324-5p 水平升高。此外,db/db 小鼠外周血和肝脏中 miR-324-5p 的表达增强。进一步的研究表明,miR-324-5p 的过表达减少了 AKT/GSK 通路的激活并增加了脂质堆积,而 miR-324-5p 的抑制则激活了 AKT/GSK 通路并减少了脂质堆积。双荧光素酶报告基因实验表明 Rho 相关卷曲螺旋蛋白激酶 1(ROCK1)是 miR-324-5p 的靶基因。此外,沉默 ROCK1 可使脂质和葡萄糖代谢恶化。更为重要的是,沉默 ROCK1 逆转了 miR-324-5p 抑制剂诱导的葡萄糖和脂质代谢改善。综上所述,miR-324-5p 通过靶向 ROCK1 在外周血中发挥对葡萄糖和脂质代谢的调节作用,而 ROCK1 参与代谢紊乱。miR-324-5p 用于诊断代谢综合征值得研究,可能对患者有益。