miR-103 Promotes Neurite Outgrowth and Suppresses Cells Apoptosis by Targeting Prostaglandin-Endoperoxide Synthase 2 in Cellular Models of Alzheimer’s Disease

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.

Circular RNA circ_0000950 promotes neuron apoptosis, suppresses neurite outgrowth and elevates inflammatory cytokines levels via directly sponging miR-103 in Alzheimer’s disease

“…Rat pheochromocytoma cell line PC12 and human embryonic kidney cells 293T cell line were purchased from Cell Resource Center of Shanghai Institute of Life Sciences, Chinese Academy of Sciences (Shanghai, China). Primary cerebral cortex neurons from rat embryo were acquired according to the methods as described in our previous study [13].…”

“…In our previous study, we observed that miR-103 promoted neurite outgrowth and suppress cell apoptosis by targeting prostaglandin-endoperoxide synthase 2 (PTGS2) in two cellular models of AD (PC12 cellular AD model and cellular AD model of rat cerebral cortex neurons), however, the upstream regulator of miR-103 in AD is still unclear [13]. According to the data retrieved from miRanda Database (http://www.microrna.…”

miR-103/miR-195/miR-15b Regulate SALL4 and Inhibit Proliferation and Migration in Glioma

“…Zheng et al reported that miR-103 enhances the proliferation of gastric cancer cells by targeting klf4 [ 39 ]. It was also found that miR-103 promotes neurite outgrowth and reduces cell apoptosis by targeting prostaglandin-endoperoxide synthase 2 (PTGS2) in cellular models of Alzheimer’s disease [ 40 ]. Recently, a few studies reported that miR-195 and miR-15b play roles that contribute to cell proliferation as oncogenes.…”

An investigation of microRNA‐103 and microRNA‐107 as potential blood‐based biomarkers for disease risk and progression of Alzheimer's disease

“…As for miR‐103 and miR‐107, a study conducted in cellular model of AD exhibited that miR‐103 promotes neurite outgrowth and suppresses cell apoptosis by targeting PTGS2 . And miR‐107 upregulation is shown to facilitate cell survival, reduce lactate dehydrogenase leakage, and inhibit apoptosis and Aβ production in AD .…”

“…Previous studies have identified that miR‐103 and miR‐107, belonging to the same family and only differ at one nucleotide residue near the 3′ end, are differentially expressed in CSF of AD patients and have evolutionary conserved binding sites for AD‐related gene, a disintegrin and metalloproteinase 10 (ADAM10) . Moreover, miR‐103 is previously shown to promote neurite outgrowth and suppresses neuron apoptosis by targeting prostaglandin‐endoperoxide synthase 2 (PTGS2) in AD . Nonetheless, the predictive value of circulating miR‐103 and miR‐107 for AD susceptibility and progression is still unknown.…”