Diagnostic value of miR-193a-3p in Alzheimer's disease and miR-193a-3p attenuates amyloid-β induced neurotoxicity by targeting PTEN

被引:37
作者
Cao, Fengjun [1 ]
Liu, Zhongjie [1 ]
Sun, Guanjun [1 ]
机构
[1] Shanxian Cent Hosp, Dept Neurol, 1 Wenhua Rd, Heze 274300, Shandong, Peoples R China
关键词
MiR-193a-3p; Alzheimer's disease; Neuroprotective; PTEN; OXIDATIVE STRESS; CELL-GROWTH; BIOMARKER; ACTIVATION; MICRORNAS; APOPTOSIS; PI3K/AKT; PATHWAY; GENE;
D O I
10.1016/j.exger.2019.110814
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Objective: Many microRNAs (miRNAs) have been reported to be aberrantly expressed in Alzheimer's disease (AD) patients. The present study aimed to explore the diagnostic value and neuroprotective role of miR-193a-3p in AD. Methods: 108 sporadic AD patients and 93 healthy controls were included. An A beta 25-35 insult cellular AD model of PC12 and SH-SY5Y was established. The relative expression levels of miR-193a-3p were calculated using qRT-PCR. Receiver operating characteristic (ROC) curve was applied to evaluate the usefulness of miR-193a-3p for detecting AD. Cell viability and apoptotic rates were calculated. Luciferase reporter assay was performed to confirm the interaction between miR-193a-3p and PTEN. Results: miR-193a-3p expression was downregulated in both AD patients and the cellular AD model (all P < 0.001). Remarkable positive association was detected between serum miR-193a-3p level and MMSE score in AD patients (r = 0.5889, P < 0.0001). The diagnostic sensitivity and specificity were 89.8% and 77.4%, respectively, and the area under the curve (AUC) was 0.914. Overexpression of miR-193a-3p weakened A beta 25-35 induced cell viability inhibition, and reduced A beta 25-35 induced cell apoptosis in PC12 cells (all P < 0.01). Downregulation of miR-193a-3p intensified the effect of A beta 25-35 PTEN was proved to be the target gene of miR-193a-3p. Conclusion: MiR-193a-3p could be a novel biomarker for AD diagnosis, and may protect against neurotoxicity in AD by targeting PTEN.
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页数:7
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共 41 条
[1]   Mini-Mental State Examination (MMSE) for the detection of Alzheimer's disease and other dementias in people with mild cognitive impairment (MCI) [J].
Arevalo-Rodriguez, Ingrid ;
Smailagic, Nadja ;
Roque i Figuls, Marta ;
Ciapponi, Agustin ;
Sanchez-Perez, Erick ;
Giannakou, Antri ;
Pedraza, Olga L. ;
Bonfill Cosp, Xavier ;
Cullum, Sarah .
COCHRANE DATABASE OF SYSTEMATIC REVIEWS, 2015, (03)
[2]   Drug treatments in Alzheimer's disease [J].
Briggs, Robert ;
Kennelly, Sean P. ;
O'Neill, Desmond .
CLINICAL MEDICINE, 2016, 16 (03) :247-253
[3]   MiR-193a-5p and-3p Play a Distinct Role in Gastric Cancer: miR-193a-3p Suppresses Gastric Cancer Cell Growth by Targeting ETS1 and CCND1 [J].
Chou, Nan-Hua ;
Lo, Yi-Hao ;
Wang, Kuo-Chiang ;
Kang, Chi-Hsiang ;
Tsai, Chung-Yu ;
Tsai, Kuo-Wang .
ANTICANCER RESEARCH, 2018, 38 (06) :3309-3318
[4]   Plasma miR-34a-5p and miR-545-3p as Early Biomarkers of Alzheimer's Disease: Potential and Limitations [J].
Cosin-Tomas, Marta ;
Antonell, Anna ;
Llado, Albert ;
Alcolea, Daniel ;
Fortea, Juan ;
Ezquerra, Mario ;
Lleo, Albert ;
Jose Marti, Maria ;
Pallas, Merce ;
Sanchez-Valle, Raquel ;
Luis Molinuevo, Jose ;
Sanfeliu, Coral ;
Kaliman, Perla .
MOLECULAR NEUROBIOLOGY, 2017, 54 (07) :5550-5562
[5]   Inhibition of PTEN Attenuates Endoplasmic Reticulum Stress and Apoptosis via Activation of PI3K/AKT Pathway in Alzheimer's Disease [J].
Cui, Weigang ;
Wang, Songtao ;
Wang, Zhongping ;
Wang, Zhiyong ;
Sun, Chunli ;
Zhang, Yinghua .
NEUROCHEMICAL RESEARCH, 2017, 42 (11) :3052-3060
[6]   A panel of four decreased serum microRNAs as a novel biomarker for early Parkinson's disease [J].
Dong, Hui ;
Wang, Cheng ;
Lu, Sunbin ;
Yu, Cuiyu ;
Huang, Lei ;
Feng, Wuruo ;
Xu, Hui ;
Chen, Xi ;
Zen, Ke ;
Yan, Qiao ;
Liu, Weiguo ;
Zhang, Chunni ;
Zhang, Chen-Yu .
BIOMARKERS, 2016, 21 (02) :129-137
[7]   Alzheimer's disease combination treatmente [J].
Fessel, Jeffrey .
NEUROBIOLOGY OF AGING, 2018, 63 :165-165
[8]   Alzheimer's and Parkinson's diseases: The prion concept in relation to assembled Aβ, tau, and α-synuclein [J].
Goedert, Michel .
SCIENCE, 2015, 349 (6248)
[9]   Biological Function of MicroRNA193a-3p in Health and Disease [J].
Grossi, Ilaria ;
Salvi, Alessandro ;
Abeni, Edoardo ;
Marchina, Eleonora ;
De Petro, Giuseppina .
INTERNATIONAL JOURNAL OF GENOMICS, 2017, 2017
[10]   A 9-microRNA Signature in Serum Serves as a Noninvasive Biomarker in Early Diagnosis of Alzheimer's Disease [J].
Guo, Rui ;
Fan, Gang ;
Zhang, Jian ;
Wu, Chunxiao ;
Du, Yifeng ;
Ye, Hui ;
Li, Zhang ;
Wang, Lili ;
Zhang, Zhihui ;
Zhang, Lu ;
Zhao, Yueran ;
Lu, Zhiming .
JOURNAL OF ALZHEIMERS DISEASE, 2017, 60 (04) :1365-1377