Differential Expression of miR-381-3p in Alzheimer’s Disease Patients and Its Role in Beta-Amyloid-Induced Neurotoxicity and Inflammation

Abstract

<b><i>Introduction:</i></b> This study aimed to explore the diagnostic value and effect of miR-381-3p on Alzheimer’s disease (AD). <b><i>Methods:</i></b> RT-qPCR was used for the measurement of miR-381-3p levels. Pearson correlation coefficient was used for the correlation analysis. Receiver operating characteristic (ROC) curve was constructed to assess the distinct ability of miR-381-3p for AD. SH-SY5Y cells were treated with Aβ25-35 to establish an AD cell model. The role of miR-381-3p on cell proliferation and apoptosis was detected. ELISA was applied to detect the protein levels of inflammatory cytokine expression. The target relationship of miR-381-3p with PTGS2 was verified by luciferase reporter gene assay. <b><i>Results:</i></b> Low expression of miR-381-3p was detected in the serum of AD patients and cell models. There was a negative association of serum miR-381-3p with the serum inflammatory cytokines. The ROC curve demonstrated the distinct ability of serum miR-381-3p for AD, with the AUC value of 0.898, with a sensitivity of 87.5%, and a specificity of 77.7%. Overexpression of miR-381-3p reversed the influence of Aβ25-35 on cell proliferation and apoptosis, but miR-381-3p downregulation exacerbated the influence. miR-381-3p overexpression inhibited the release of IL-6, IL-1β, and TNF-α induced by Aβ25-35 treatment, whereas miR-381-3p downregulation further promoted the release of inflammatory cytokines. PTGS2 was the target gene of miR-381-3p and was upregulated in AD cell models. <b><i>Conclusion:</i></b> miR-381-3p is less expressed in the serum of AD patients and has potential diagnostic values for AD. Overexpression of miR-381-3p may attenuate Aβ25-35-induced neurotoxicity and inflammatory responses via targeting PTGS2 in SH-SY5Y cells.

Suicide and Changes in Expression of Neuronal miRNA Predicted by an Algorithm Search through miRNA Databases

“…The second miRNA we observed with a trend towards significance, hsa-miR-381-3p, has not yet been associated with suicidality. A study did, however, observe hsa-miR-381-3p as potentially involved in brain state and inflammation, where a decreased expression of has-miR-381-3p was observed in the serum of patients with Alzheimer's disease [41]. Taking both hsa-miR-4516 and has-miR-381-3p into account, together they target too few genes to look at a common gene ontology assessment.…”

NcRNAs: A synergistically antiapoptosis therapeutic tool in Alzheimer's disease

“…MiR‐485‐3p‐CD36 axis weakened the phagocytosis of Aβ in vitro and in vivo and might promote cell apoptosis in AD 138 . Table S3 summarizes all the abnormally expressed and cell apoptosis‐related miRNAs in AD patients 132–160 . These miRNAs can form ‘miRNA‐mRNA’ axis in regulating cell apoptosis in AD.…”

“… 138 Table S3 summarizes all the abnormally expressed and cell apoptosis‐related miRNAs in AD patients. 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 These miRNAs can form ‘miRNA‐mRNA’ axis in regulating cell apoptosis in AD.…”

MicroRNAs-Based Theranostics against Anesthetic-Induced Neurotoxicity

“…The report of neurotoxicity induced by anesthetics and heavy metals included in the study was based on animal models and cell lines. Contrary to this, evidence of neurotoxicity related to Alzheimer’s disease (AD) and Parkinson’s disease (PD) originated from studies in animal models, cell lines as well as plasma, serum, peripheral blood, and cerebrospinal fluid (CSF) [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”