Lower Serum Levels of miR-29c-3p and miR-19b-3p as Biomarkers for Alzheimer’s Disease

Lower Serum Levels of miR-29c-3p and miR-19b-3p as Biomarkers for Alzheimer's Disease

YUQUAN WU,^1,2 JUAN XU,² JING XU,² JUN CHENG,³ DEMIN JIAO,³ CHUN ZHOU,² YI DAI² and QINGYONG CHEN²

¹The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, P.R. China
²Department of Geriatrics, the 117th Hospital of the Chinese People's Liberation Army (PLA), Hangzhou, Zhejiang, P.R. China
³Department of Clinical Laboratory, the 117th Hospital of the Chinese People's Liberation Army (PLA), Hangzhou, Zhejiang, P.R. China

MicroRNAs (miRNAs) are short noncoding RNA that participate in posttranscriptional gene regulation. However, little is understood about the roles of miRNAs in Alzheimer's disease (AD). In this study, we used next-generation sequencing on RNA extracted from the serum samples of 20 AD patients and 20 controls, yielding a total of 72 miRNAs with significantly changed expression levels. Among these candidates, we selected 9 miRNAs with most significant alteration in disease, and validated their expression levels using RT-qPCR analysis on serum samples from 45 AD patients and 40 control subjects. Thus, the serum levels of miR-146a-5p, 106b-3p, 195-5p, 20b-5p, and 497-5p were significantly higher, while those of miR-125b-3p, 29c-3p, 93-5p and 19b-3p were significantly lower in AD patients, compared with control subjects. Two miRNAs, miR-29c-3p and miR-19b-3p, were selected because both RNA deep-sequencing and q-PCR methods indicated lower serum levels of these miRNAs in AD patients. Computational analysis predicted that 3'-untranslated region of signal transduction and activator of transcription 3 (STAT3) mRNA is targeted both by miR-29c-3p and miR-19b-3p. Using SH-SY5Y human neuroblastoma cells, we showed that transfection with miR-29c-3p or miR-19b-3p inhibitor significantly increased STAT3 phosphorylation. Furthermore, Water maze test, which assesses the learning and memory deficits in rodents, showed that escape latency was significantly shorter in AD rats with overexpression of miR-29c-3p or miR-19b-3p than in control AD rats. These results suggest that miR-29c-3p or miR-19b-3p may contribute to the cognitive function. In conclusion, the serum levels of miR-29c-3p and miR-19b-3p are helpful biomarkers for AD.

keywords —— Alzheimer's disease; microRNA; miR-19b-3p; miR-29c-3p; STAT3

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Tohoku J. Exp. Med., 2017, 242, 129-136

Correspondence: Yuquan Wu, Department of Geriatrics, the 117th Hospital of the Chinese People's Liberation Army (PLA), 14 Ling-yin Road, Hangzhou, Zhejiang 310013, P.R. China.

e-mail: hz117wyq@163.com