Identification of miRNA–mRNA Pairs in the Alzheimer’s Disease Expression Profile and Explore the Effect of miR-26a-5p/PTGS2 on Amyloid-β Induced Neurotoxicity in Alzheimer’s Disease Cell Model
Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common type of dementia. MicroRNAs (miRNAs) have been extensively studied in many diseases, including AD. To identify the AD-specific differentially expressed miRNAs and mRNAs, we used bioinformatics analysis to study c...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2022.909222/full |
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| author | Tao Xie Yongyan Pei Peijia Shan Qianqian Xiao Fei Zhou Liuqing Huang Shi Wang |
| author_facet | Tao Xie Yongyan Pei Peijia Shan Qianqian Xiao Fei Zhou Liuqing Huang Shi Wang |
| author_sort | Tao Xie |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common type of dementia. MicroRNAs (miRNAs) have been extensively studied in many diseases, including AD. To identify the AD-specific differentially expressed miRNAs and mRNAs, we used bioinformatics analysis to study candidate miRNA–mRNA pairs involved in the pathogenesis of AD. These miRNA–mRNAs may serve as promising biomarkers for early diagnosis or targeted therapy of AD patients. In this study, based on the AD mRNA and miRNA expression profile data in Gene Expression Omnibus (GEO), through differential expression analysis, functional annotation and enrichment analysis, weighted gene co-expression network analysis, miRNA–mRNA regulatory network, protein–protein interaction network, receiver operator characteristic and Least absolute shrinkage and selection operator (LASSO) regression and other analysis, we screened the key miRNA–mRNA in the progress of AD: miR-26a-5p/PTGS2. Dual-luciferase and qPCR experiments confirmed that PTGS2 is a direct target gene of miR-26a-5p. The expression of miR-26a-5p in the peripheral blood of AD patients and AD model cells (SH-SY5Y cells treated with Aβ25–35) was up-regulated, and the expression of PTGS2 was down-regulated. Functional gain -loss experiments confirmed that PTGS2 protects AD model cells from damage by inhibiting proliferation and migration. However, the expression of miR-26a-5p promotes the proliferation of AD model cells. It is further found that PTGS2 is involved in the regulation of miR-26a-5p and can reverse the effect of miR-26a-5p on the proliferation of AD model cells. In addition, through network pharmacology, qPCR and CCK-8, we found that baicalein may affect the progression of AD by regulating the expression of PTGS2. Therefore, PTGS2 can be used as a target for AD research, and miR-26a-5p/PTGS2 can be used as an axis of action to study the pathogenesis of AD. |
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| language | English |
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| spelling | doaj.art-caf5272a2628457fb61740a5f58904512022-12-22T00:28:02ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-06-011410.3389/fnagi.2022.909222909222Identification of miRNA–mRNA Pairs in the Alzheimer’s Disease Expression Profile and Explore the Effect of miR-26a-5p/PTGS2 on Amyloid-β Induced Neurotoxicity in Alzheimer’s Disease Cell ModelTao Xie0Yongyan Pei1Peijia Shan2Qianqian Xiao3Fei Zhou4Liuqing Huang5Shi Wang6Department of Neurology, The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaSchool of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan, ChinaDepartment of Neurology, Changhai Hospital, Naval Medical University, Shanghai, ChinaDepartment of Neurology, The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Neurology, The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Neurology, The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Neurology, The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaAlzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common type of dementia. MicroRNAs (miRNAs) have been extensively studied in many diseases, including AD. To identify the AD-specific differentially expressed miRNAs and mRNAs, we used bioinformatics analysis to study candidate miRNA–mRNA pairs involved in the pathogenesis of AD. These miRNA–mRNAs may serve as promising biomarkers for early diagnosis or targeted therapy of AD patients. In this study, based on the AD mRNA and miRNA expression profile data in Gene Expression Omnibus (GEO), through differential expression analysis, functional annotation and enrichment analysis, weighted gene co-expression network analysis, miRNA–mRNA regulatory network, protein–protein interaction network, receiver operator characteristic and Least absolute shrinkage and selection operator (LASSO) regression and other analysis, we screened the key miRNA–mRNA in the progress of AD: miR-26a-5p/PTGS2. Dual-luciferase and qPCR experiments confirmed that PTGS2 is a direct target gene of miR-26a-5p. The expression of miR-26a-5p in the peripheral blood of AD patients and AD model cells (SH-SY5Y cells treated with Aβ25–35) was up-regulated, and the expression of PTGS2 was down-regulated. Functional gain -loss experiments confirmed that PTGS2 protects AD model cells from damage by inhibiting proliferation and migration. However, the expression of miR-26a-5p promotes the proliferation of AD model cells. It is further found that PTGS2 is involved in the regulation of miR-26a-5p and can reverse the effect of miR-26a-5p on the proliferation of AD model cells. In addition, through network pharmacology, qPCR and CCK-8, we found that baicalein may affect the progression of AD by regulating the expression of PTGS2. Therefore, PTGS2 can be used as a target for AD research, and miR-26a-5p/PTGS2 can be used as an axis of action to study the pathogenesis of AD.https://www.frontiersin.org/articles/10.3389/fnagi.2022.909222/fullAlzheimer’s diseasemiRNA–mRNAmiR-26a-5p/PTGS2neurotoxicitybaicalein |
| spellingShingle | Tao Xie Yongyan Pei Peijia Shan Qianqian Xiao Fei Zhou Liuqing Huang Shi Wang Identification of miRNA–mRNA Pairs in the Alzheimer’s Disease Expression Profile and Explore the Effect of miR-26a-5p/PTGS2 on Amyloid-β Induced Neurotoxicity in Alzheimer’s Disease Cell Model Frontiers in Aging Neuroscience Alzheimer’s disease miRNA–mRNA miR-26a-5p/PTGS2 neurotoxicity baicalein |
| title | Identification of miRNA–mRNA Pairs in the Alzheimer’s Disease Expression Profile and Explore the Effect of miR-26a-5p/PTGS2 on Amyloid-β Induced Neurotoxicity in Alzheimer’s Disease Cell Model |
| title_full | Identification of miRNA–mRNA Pairs in the Alzheimer’s Disease Expression Profile and Explore the Effect of miR-26a-5p/PTGS2 on Amyloid-β Induced Neurotoxicity in Alzheimer’s Disease Cell Model |
| title_fullStr | Identification of miRNA–mRNA Pairs in the Alzheimer’s Disease Expression Profile and Explore the Effect of miR-26a-5p/PTGS2 on Amyloid-β Induced Neurotoxicity in Alzheimer’s Disease Cell Model |
| title_full_unstemmed | Identification of miRNA–mRNA Pairs in the Alzheimer’s Disease Expression Profile and Explore the Effect of miR-26a-5p/PTGS2 on Amyloid-β Induced Neurotoxicity in Alzheimer’s Disease Cell Model |
| title_short | Identification of miRNA–mRNA Pairs in the Alzheimer’s Disease Expression Profile and Explore the Effect of miR-26a-5p/PTGS2 on Amyloid-β Induced Neurotoxicity in Alzheimer’s Disease Cell Model |
| title_sort | identification of mirna mrna pairs in the alzheimer s disease expression profile and explore the effect of mir 26a 5p ptgs2 on amyloid β induced neurotoxicity in alzheimer s disease cell model |
| topic | Alzheimer’s disease miRNA–mRNA miR-26a-5p/PTGS2 neurotoxicity baicalein |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2022.909222/full |
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