Dong Li-Hua, Sun Lei, Zhang Wen-Jing, Wang Xiao-Yan, Li Jia-Mei
Department of Neurology, Rizhao People's Hospital, Rizhao City, Shandong Province, China.
Kaohsiung J Med Sci. 2021 Aug;37(8):730-738. doi: 10.1002/kjm2.12391. Epub 2021 May 27.
The current study investigated whether the expression of miR-202 was abnormal in the serum of patients with Alzheimer's disease (AD) and evaluated the potential clinical significance, thereby shedding light on the diagnosis of AD. Here, our data showed that the level of miR-202 decreased significantly in the serum of AD patients (n = 121) compared with that of healthy controls (n = 86). Further analysis showed that the level of serum miR-202 was gradually decreased in the mild AD group (n = 31), moderate AD group (n = 52) and severe AD group (n = 38) compared with the healthy control group. Receiver operating characteristic (ROC) curve analysis demonstrated that serum miR-202 could differentiate AD patients from healthy controls, with an AUC of 0.892. Spearman correlation analysis showed that serum miR-202 was positively correlated with the Mini-Mental State Examination (MMSE). Based on TargetScan, a conserved binding site was identified in the 3'UTR of amyloid precursor protein (APP). The dual luciferase assay showed that miR-202 suppressed the relative luciferase activity of pmirGLO-APP-3'UTR. Western blot assays indicated that overexpression of miR-202 suppressed the expression of APP, while the expression of APP was enhanced after inhibition of miR-202 in PC12 cells, indicating that APP was a possible target gene of miR-202. Moreover, the cell apoptosis induced by transfection of miR-202 inhibitor was abolished by silencing APP. In summary, we showed novel data that downregulation of serum miR-202 may be used as a potential biomarker for AD and may promote the development of AD by targeting APP.
本研究调查了阿尔茨海默病（AD）患者血清中miR-202的表达是否异常，并评估其潜在的临床意义，从而为AD的诊断提供线索。在此，我们的数据显示，与健康对照组（n = 86）相比，AD患者（n = 121）血清中miR-202水平显著降低。进一步分析表明，与健康对照组相比，轻度AD组（n = 31）、中度AD组（n = 52）和重度AD组（n = 38）血清miR-202水平逐渐降低。受试者工作特征（ROC）曲线分析表明，血清miR-202可区分AD患者和健康对照组，曲线下面积（AUC）为0.892。Spearman相关性分析表明，血清miR-202与简易精神状态检查表（MMSE）呈正相关。基于TargetScan，在淀粉样前体蛋白（APP）的3'非翻译区（UTR）中鉴定出一个保守的结合位点。双荧光素酶测定表明，miR-202抑制了pmirGLO-APP-3'UTR的相对荧光素酶活性。蛋白质免疫印迹分析表明，miR-202过表达抑制了APP的表达，而在PC12细胞中抑制miR-202后APP的表达增强，表明APP可能是miR-202的靶基因。此外，沉默APP可消除转染miR-202抑制剂诱导的细胞凋亡。总之，我们展示了新的数据，即血清miR-202的下调可能作为AD的潜在生物标志物，并可能通过靶向APP促进AD的发展。
