MicroRNA-384 regulates both amyloid precursor protein and β-secretase expression and is a potential biomarker for Alzheimer's disease.
Amyloid precursor protein (APP) and β-site APP cleaving enzyme (BACE-1) play important roles in the pathogenesis of Alzheimer's disease (AD). In this study, using bioinformatics analysis, we demonstrate that miR-384 is a microRNA (miRNA or miR) predicted to potentially target the 3' untranslated regions (3'-UTRs) of both APP and BACE-1. SH-SY5Y cells were transfected with miR-384 mimic oligonucleotide, miR-384 inhibitor oligonucleotide, or a non-specific control siRNA. We found that the overexpression of miR-384 suppressed the mRNA and protein expression of both APP and BACE-1. The miR-384 inhibitor oligonucleotide induced the upregulation of APP and BACE-1. The activity of BACE-1 was altered following the change in its protein expression. The binding sites of miR-384 on the 3'-UTRs of APP and BACE-1 were identified by luciferase assay. Furthermore, cells were treasted with amyloid-β (Aβ)42. Aβ42 downregulated miR-384 expression, leading to the continuous reduction in miR-384 expression. In addition, using a mouse model of AD, as well as patients with mild cognitive impairment (MCI) and dementia of Alzheimer's type (DAT), we examined the levels of miR-384 in cerebral spinal fluid (CSF) and serum. Patients with MCI and DAT had lower blood miR-384 levels compared with the controls. In addition, patients with DAT had lower blood miR-384 levels in blood compared with the MCI group. We also found decreased miR-384 expression in the several cerebral spinal fluid (CSF) of the patients with DAT. Negative correlations were observed between miR-384 and Aβ42 in the serum and CSF from patients with AD. In conclusion, these findings demonstrate that miR-384 may plays a role in the development of AD and may be a potential non-invasive biomarker for the diagnosis of AD.
Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Chen-Geng
CG
Liu
Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Jin-Ling
JL
Wang
Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Lei
L
Li
Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Pei-Chang
PC
Wang
D020413:3' Untranslated Regions; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D060825:Cognitive Dysfunction / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction
D020413:3' Untranslated Regions; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D035683:MicroRNAs; D010446:Peptide Fragments; D034741:RNA, Small Interfering; C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C509282:Bace1 protein, mouse