MiR‐483‐3p improves learning and memory abilities via XPO1 in Alzheimer's disease

Luo, Gang; Wang, Xiaoyan; Liu, Changya

doi:10.1002/brb3.2680

Cited by 7 publications

(3 citation statements)

References 120 publications

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“…Dysregulated miRNAs, including miR-106b ( 36 ), miR-196a ( 37 ), and miR-124 ( 15 ), are important factors in the development of many degenerative diseases ( 41 , 42 ). For example, recent studies have shown that low levels of miRNAs miR-27a-3p ( 43 ) and high levels of miR-483-3p ( 44 ) can promote the development of AD. Moreover, miR-342-3p ( 45 ) and miR-103a-3p ( 46 ) affect the occurrence and subsequent stages of AD.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-668-3p regulates oxidative stress and cell damage induced by Aβ1-42 by targeting the OXR1/p53-p21 axis

Li¹,

Wu²,

Ma³

et al. 2022

Ann Transl Med

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Background Alzheimer’s disease (AD) is the most common type of dementia in old age and has become a serious social and medical problem threatening human health. We aimed to explore the mechanisms underlying AD development by screening for microRNAs (miRNAs) that affect AD progression and examining their role in AD development. Methods Hematoxylin-eosin (HE) staining, immunohistochemistry, and immunofluorescence (IF) were used to analyze the characteristics of the hippocampus, neuron cell separation, and related protein expression in mice. We used Gene Expression Omnibus (GEO) data analysis to screen miRNAs and mRNAs that affect AD progression, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot analysis to determine changes in miRNA and mRNA levels before and after amyloid β (Aβ)1-42 induction. In addition, we used luciferase analysis to examine miRNA and mRNA binding and the effect of miRNA/mRNA interaction on neuronal cell proliferation. Apoptosis and reactive oxygen species (ROS) levels were examined using Cell Counting Kit-8 analysis and flow cytometry (FCM), respectively. The enzyme-linked immunosorbent assay was used to analyze changes in neuronal cell-secreted oxidative stress-related protein levels through miRNA/mRNA interaction. Results Oxidative stress levels were significantly increased in the AD mouse model. GEO data analysis revealed 67 dysregulated miRNAs, and miR-668-3p was identified as a potential therapeutic target for AD. We found that the AD and Aβ1-42-induced models showed an increase in miR-668-3p and a decrease in oxidation resistance 1 ( OXR1 ) expression. The luciferase analysis results revealed that miR-668-3p may play a role in AD development by targeting OXR1 and promoting intracellular oxidative stress by activating p53-p21 signaling. The final rescue experiment also confirmed that Aβ1-42-induction decreased cell proliferation, increased apoptosis, increased cell cycle arrest, and promoted oxidative stress. Tenovin-1 (TEN) enhanced the effect of Aβ1-42, and the miR-668-3p inhibitor partially alleviated it, although the effect of the miR-668-3p inhibitor was weakened by TEN. Conclusions MiR-668-3p negatively regulated OXR1 expression by targeting OXR1 , affecting p53-p21 protein signaling, and regulating cell damage and oxidative stress induced by Aβ1-42. Therefore, miR-668-3p may be a potential therapeutic target for AD.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-668-3p regulates oxidative stress and cell damage induced by Aβ1-42 by targeting the OXR1/p53-p21 axis

Li¹,

Wu²,

Ma³

et al. 2022

Ann Transl Med

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“…MiR‐132‐3p‐MAPK1 axis and miR‐132‐3p‐HNRNPU axis inhibited cell apoptosis in the AD rat models 85,86 . Table S2 summarizes all the cell apoptosis‐related and abnormally expressed miRNAs in multiple AD animal models 80,81,83–120 . These miRNAs can form ‘miRNA‐mRNA’ axis in regulating cell apoptosis in AD.…”

Section: Abnormally Expressed Ncrnas In Ad Animal Models In Regulatin...mentioning

confidence: 99%

“… 85 , 86 Table S2 summarizes all the cell apoptosis‐related and abnormally expressed miRNAs in multiple AD animal models. 80 , 81 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 These miRNAs can form ‘miRNA‐mRNA’ axis in regulating cell apoptosis in AD.…”

Section: Abnormally Expressed Ncrnas In Ad Animal Models In Regulatin...mentioning

confidence: 99%

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

Li,

Jin,

Tan

et al. 2023

CNS Neurosci Ther

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AimsThe aim of this review is to systematically summarize and analyze the noncoding RNAs (ncRNAs), especially microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), in the cell apoptosis among Alzheimer's disease (AD) in recent years to demonstrate their value in the diagnosis and treatment of AD.MethodsWe systematically summarized in vitro and in vivo studies focusing on the ncRNAs in the regulation of cell apoptosis among AD in PubMed, ScienceDirect, and Google Scholar.ResultsWe discover three patterns of ncRNAs (including ‘miRNA‐mRNA’, ‘lncRNA‐miRNA‐mRNA’, and ‘circRNA‐miRNA‐mRNA’) form the ncRNA‐based regulatory networks in regulating cell apoptosis in AD.ConclusionsThis review provides a future diagnosis and treatment strategy for AD patients based on ncRNAs.

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MiR‐483‐3p improves learning and memory abilities via XPO1 in Alzheimer's disease

2022

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Introduction Alzheimer's disease (AD), a common form of dementia, has been reported to influence 27 million individuals globally. Several risk factors including oxidative stress, gut microbiota imbalance, and cognitive activity are reported to be closely associated with the initiation or progression of AD. Although miR‐483‐3p was identified to be downregulated in AD patient serum. However, the biological role and mechanism of miR‐483‐3p remained unknown in AD. Here, we explored the role of miR‐483‐3p in AD. Methods Sprague–Dawley rats were injected with homocysteine (Hcy) to establish an AD animal model. The Morris water maze tests and contextual fear tests were conducted to assess the cognitive and memory abilities of rats. TUNEL staining was utilized to determine cell apoptosis. Luciferase reporter assay was used to evaluate the binding relation between miR‐483‐3p and exportin 1 (XPO1). Results Homocysteine treatment (400 μg/kg) induced the learning, cognitive and memory defects of rats. miR‐483‐3p was downregulated in Hcy‐treated rat hippocampus. Functionally, miR‐483‐3p alleviated cell apoptosis and impairments of learning and memory abilities in Hcy‐treated rats. In addition, miR‐483‐3p inhibited cell apoptosis and protein level of AD‐associated factors (APP, BACE1, and Aβ1‐42) in PC12 cells. In mechanism, miR‐483‐3p was confirmed to target XPO1 in PC12 cells. XPO1 displayed high level in rat hippocampus and was negatively correlated with miR‐483‐3p levels. Finally, XPO1 overexpression rescued the suppressive effect of miR‐483‐3p on cell apoptosis and protein levels of AD‐associated factors. Conclusions miR‐483‐3p alleviates neural cell apoptosis and impairments of learning and memory abilities by targeting XPO1 in AD.

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MiR‐483‐3p improves learning and memory abilities via XPO1 in Alzheimer's disease

Cited by 7 publications

References 120 publications

MicroRNA-668-3p regulates oxidative stress and cell damage induced by Aβ1-42 by targeting the OXR1/p53-p21 axis

MicroRNA-668-3p regulates oxidative stress and cell damage induced by Aβ1-42 by targeting the OXR1/p53-p21 axis

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

MiR‐483‐3p improves learning and memory abilities via XPO1 in Alzheimer's disease

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