Abstract
miR-103 has been reported to be decreased in brain of transgenic mouse model of Alzheimer’s disease (AD) and in cerebrospinal fluid (CSF) of AD patients, while the detailed mechanism of its effect on AD is obscure, thus this study aimed to investigate the effect of miR-103 expression on neurite outgrowth and cells apoptosis as well as its targets in cellular models of AD. Blank mimic (NC1-mimic), miR-103 mimic, blank inhibitor (NC2-mimic) and miR-103 inhibitor plasmids were transferred into PC12 cellular AD model and Cellular AD model of cerebral cortex neurons which were established by Aβ1–42 insult. Rescue experiment was subsequently performed by transferring Prostaglandin-endoperoxide synthase 2 (PTGS2) and miR-103 mimic plasmid. mRNA and protein expressions were detected by qPCR and Western Blot assays. Total neurite outgrowth was detected by microscope, cells apoptosis was determined by Hoechst/PI assay, and apoptotic markers Caspase 3 and p38 expressions were determined by Western Blot assay. In both PC12 and cerebral cortex neurons cellular AD models, miR-103 mimic increases the total neurite outgrowth compared with NC1-mimic, while miR-103 inhibitor decreases the total neurite outgrowth than NC2-inhibitor. The apoptosis rate was decreased in miR-103 mimic group than NC1-mimic group while increased in miR-103 inhibitor group than NC2-inhibitor group. PTGS2, Adisintegrin and metalloproteinase 10 (ADAM10) and neprilysin (NEP) were selected as target genes of miR-103 by bioinformatics analysis. And PTGS2 was found to be conversely regulated by miR-103 expression while ADAM10 and NEP were not affected. After transfection by PTGS2 and miR-103 mimic plasmid in PC12 cellular AD model, the total neurite growth was shortened compared with miR-103 mimic group, and cells apoptosis was enhanced which indicated PTGS2 mimic attenuated the influence of miR-103 mimic on progression of AD. In conclusion, miR-103 promotes total neurite outgrowth and inhibits cells apoptosis by targeting PTGS2 in cellular models of AD.
Highlights
Alzheimer’s disease (AD), characterized by neurofibrillary tangles and amyloid β (Aβ) deposits, is one of the most challenging diseases to human health which presents with impaired cognition, memory and language as well as dementia (Chan et al, 2013; Scheltens et al, 2016)
After construction of AD models, we detected the miR-103 expression between AD models and normal neurons, which illuminated that miR-103 level was decreased in AD models compared to controls in both PC12 cellular AD model (Figure 1C) and cellular AD model of cerebral cortex neurons (Figure 1D)
We found total neurite outgrowth was elevated in miR-103 mimic group compared to NC1-mimic group, while shortened in miR-103 inhibitor group compared with NC2-inhibitor group in both PC12 cellular AD model (Figure 3C) and cellular AD model of cerebral cortex neurons (Figure 3D)
Summary
Alzheimer’s disease (AD), characterized by neurofibrillary tangles and amyloid β (Aβ) deposits, is one of the most challenging diseases to human health which presents with impaired cognition, memory and language as well as dementia (Chan et al, 2013; Scheltens et al, 2016). Growing evidences disclose that AD affects a great amount of patients worldwide, it’s estimated that 3.12% of total population in United States and 5.05% population in Europe suffer from AD (Beydoun et al, 2015; Niu et al, 2017). A case-control study discloses that 74 up-regulated and 74 down-regulated miRNAs in cerebrospinal fluid (CSF) of AD patients compared to health controls are discovered (Denk et al, 2015). 20 up-regulated and 32 down-regulated miRNAs are identified in peripheral blood of AD patients by systemic analysis in a recent meta-analysis study (Wu et al, 2016). These indicate miRNAs play crucial functions in AD development and progression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
