Silenced lncRNA H19 and up-regulated microRNA-129 accelerates viability and restrains apoptosis of PC12 cells induced by Aß25-35 in a cellular model of Alzheimer's disease.

Accumulating data manifest that long non-coding RNA (lncRNAs) are involved in all kinds of neurodegenerative disorders, consisting of the onset and progression of Alzheimer's disease (AD). The study was for the research of the mechanism of lncRNA H19 (H19) in viability and apoptosis of PC12 cells induced by Aß25-35 in a cellular model of AD with the regulation of microRNA (miR)-129 and high mobility group box-1 protein (HMGB1). An AD cellular model of PC12 cells was established using Aß25-35. The Aß25-35-induced PC12 cells were transfected with si-H19 or miR-129 mimic to figure their roles in cell viability,apoptosis, mitochondrial membrane potential dysfunction and oxidative stress in AD. Luciferase reporter assay and RNA-pull down assay were employed for verification of the binding relationship between H19 and miR-129 and the targeting relationship between miR-129 and HMGB1. An AD mouse model was induced and brain tissues were collected. H19, miR-129 and HMGB1 were detected in Aß25-35-treated cells and brain tissues of AD mice. Elevated H19, HMGB1 and decreased miR-129 were found in Aß25-35-treated PC12 cells as well as in brain tissues of AD mice. Silenced H19 or elevated miR-129 promoted viability, inhibited apoptosis, prevented mitochondrial membrane potential dysfunction and decreased oxidative stress in Aß25-35-treated PC12 cells. H19 could specifically bind to miR-129. MiR-129 specifically suppressed HMGB1 expression. This study suggests that silenced H19 and up-regulated miR-129 accelerates viability and represses apoptosis of PC12 cells stimulated by Aß25-35 in AD, which is beneficial for AD treatment.

LncRNA NEAT1 promotes Alzheimer's disease by down regulating micro-27a-3p.

OBJECTIVE: Alzheimer's disease (AD) is a common neurodegenerative disease. This study was designed to investigate the roles of lncRNA NEAT1/miR-27a-3p axis in AD. METHODS: Amyloid protein was used to treat SH-SY5Y cells and rats to construct AD model. RT-qPCR was used to quantify lncRNA NEAT1 and micro-27a-3p in AD model cells. Western blot was used to determine the ß-amyloid-precursor-protein-cleaver-enzyme 1 (BACE1), amyloid, Tau protein and its phosphorylation, Caspase 3 protein and its lytic cell protein and amyloid precursor protein (APP). Flow cytometry was used to detect apoptosis. The cell activity was detected by CCK-8. The lncRNA NEAT1 and miR-27a-3p inhibition or over-expression vectors were constructed. The dual luciferase reporter gene and RNA pull-down assay were used to detect the targeting relationship between lncRNA NEAT1 and micro-27a-3p. The cognitive function of rats was tested by water maze. RESULTS: After being induced by amyloid protein, lncRNA NEAT1 was up-regulated while micro-27a-3p was down-regulated in SH-SY5Y cells. Apoptosis rate was increased and cell activity was decreased. Amyloid protein, BACE1 protein, APP protein, Tau protein and its phosphorylation, Caspase 3 protein and its lytic cell protein were up-regulated. Down-regulation of lncRNA NEAT1 or up-regulation of micro-27a-3p could reduce cell apoptosis, increase cell activity, down-regulate amyloid protein, BACE1 protein, APP protein, Tau protein and its phosphorylation, and up-regulate caspase 3 protein and its lysate protein. Dual luciferase reporter gene assay and RNA pull-down experiments revealed that micro-27a-3p was the target gene of lncRNA NEAT1. Down-regulation of micro-27a-3p could offset the changes caused by LncRNA NEAT1. AD caused cognitive dysfunction in rats, which was improved by down-regulation of lncRNA NEAT1. CONCLUSION: lncRNA NEAT1 regulates the development of AD by down-regulating micro-27a-3p.

RETRACTED: MicroRNA-16-5p/BTG2 axis affects neurological function, autophagy and apoptosis of hippocampal neurons in Alzheimer's disease.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief as there are concerns about the reliability of the results. Concerns have been raised about the western blot bands in Figures 6 B + D having the same eyebrow shaped phenotype as found in many other publications as detailed here (https://pubpeer.com/publications/B32F93859FBAA13471ED0FFCA5BCB6). The journal requested the corresponding author to comment on these concerns and send the raw data, however the author was not able to provide uncropped images of the original gels. The Editor-in-Chief therefore no longer has confidence in the data and conclusions of this study.

Inhibition of interleukin-1ß plays a protective role in Alzheimer's disease by promoting microRNA-9-5p and downregulating targeting protein for xenopus kinesin-like protein 2.

OBJECTIVE: Evidences have indicated that interleukin-1ß (IL-1ß) and microRNAs (miRNAs) are implicated in Alzheimer's disease (AD), and we aimed to study the role of IL-1ß in AD development with the involvement of miR-9-5p and targeting protein for xenopus kinesin-like protein 2 (TPX2). METHODS: APPswe/PS1dE9 double transgenic mice and C57BL/6 wild type mice were treated with inhibited IL-1ß, miR-9-5p mimic and/or silenced TPX2. Expression of IL-1ß, miR-9-5p, TPX2, amyloid-ß (Aß) and p-tau in mouse hippocampal tissues was determined. The behavioral changes, hippocampal pathological injury, Aß plaque deposition, tau expression, neuronal apoptosis and oxidative stress of AD mice were all measured. The regulatory relationships between IL and 1ß and miR-9-5p, and between miR-9-5p and TPX2 were confirmed. RESULTS: IL-1ß and TPX2 were upregulated while miR-9-5p was downregulated in hippocampal tissues from AD mice versus non-transgenic littermate mice. Inhibited IL-1ß or elevated miR-9-5p improved behavioral changes and neuronal injury of AD mice, and suppressed plaque deposition and oxidative stress in hippocampal tissues of AD mice. These changes that induced by elevated miR-9-5p could be reversed by overexpression of TPX2. IL-1ß negatively regulated miR-9-5p, and TPX2 was a target gene of miR-9-5p. CONCLUSION: This study suggested that inhibition of IL-1ß played a protective role in AD by promoting miR-9-5p and downregulating TPX2, which may contribute to exploration on AD treatment.