阿尔茨海默病患者血液中miRNA-3200-3p生物信息学分析
Bioinformatics Analysis of miRNA-3200-3p in Blood of Patients with Alzheimer’s Disease
DOI: 10.12677/acm.2024.1451612, PDF,   
作者: 闫林娜, 张 鑫, 王梓炫*：青岛大学附属医院老年医学科，山东 青岛
关键词: 阿尔茨海默病；miRNA；生物信息学；GEO；Alzheimer’s Disease； miRNA； Bioinformatics； GEO
摘要: 目的：通过生物信息学方法，探讨阿尔茨海默病(AD)患者血液中差异表达微小RNA (miRNA)的生物学功能。方法：通过基因表达综合数据库(GEO)获取AD相关的数据集GSE46579，筛选AD患者血液中差异表达miRNAs，运用在线数据库TargetScan、miRDB及Starbase预测所选miRNA的靶基因，通过GSE97760数据集筛选差异表达基因，对差异表达靶基因进行分析。运用R软件进行基因本体论(GO)和分析和京都基因与基因组百科全书(KEGG)通路分析。通过String在线网站构建蛋白互作(PPI)网络，利用Cytoscape筛选5个关键基因。结果：共筛选出56个差异表达miRNAs，其中42个下调，14个上调。23个靶基因与差异表达基因重叠。GO和KEGG富集分析显示miRNA-3200-3p靶基因参与DNA分子结构与功能变化、神经元发育和突触传递等功能，以及流体剪切应力与动脉粥样硬化信号通路和丁酸代谢等信号通路。miRNA-3200-3p调控的5个关键基因为SRSF1、CHD1、ZRANB2、PURA和KDM5C。结论：miRNA-3200-3p可能在AD的发病机制中发挥重要作用，miRNA-3200-3p可能是AD潜在的生物标志物和治疗靶点。
Abstract: Objective: To explore the biological functions of differentially expressed microRNAs (miRNAs) in the blood of Alzheimer’s disease (AD) patients by bioinformatics analysis. Methods: Dataset GSE46579 were collected from the Gene Expression Omnibus (GEO) database. We selected differentially expressed miRNA in blood patients with AD, and online databases TargetScan, miRDB and Starbase were used to predict the target genes of selected miRNAs. Differentially expressed genes were selected from the GSE97760 dataset, and analyzing the differentially expressed target genes. R software was used for gene ontology (GO) and analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Constructing protein-protein interaction (PPI) networks through the String online website and utilizing Cytoscape to filter out five key genes. Results: A total of 56 differentially expressed miRNAs were screened, with 42 downregulated and 14 upregulated. Among them, 23 target genes overlapped with the differentially expressed genes. GO and KEGG enrichment analysis revealed that the target genes of miRNA-3200-3p are involved in functions such as DNA molecular structure and functional changes, neuronal development, synaptic transmission, as well as fluid shear stress and atherosclerosis signaling pathways, and Butanoate metabolism. The five key genes regulated by miRNA-3200-3p are SRSF1, CHD1, ZRANB2, PURA, and KDM5C. Conclusions: miRNA-3200-3p may play an important role in the pathogenesis of AD, and miRNA-3200-3p may be a potential biomarker and therapeutic target for AD.
文章引用：闫林娜, 张鑫, 王梓炫. 阿尔茨海默病患者血液中miRNA-3200-3p生物信息学分析[J]. 临床医学进展, 2024, 14(5): 1746-1755. https://doi.org/10.12677/acm.2024.1451612

参考文献

[1] 徐勇, 王军, 王虹峥, 等. 2023中国阿尔茨海默病数据与防控策略[J]. 阿尔茨海默病及相关病, 2023, 6(3): 175-192.
[2] Abdelmaksoud, N.M., Sallam, A.M., Abulsoud, A.I., et al. (2024) Unraveling the Role of MiRNAs in the Diagnosis, Progression, and Therapeutic Intervention of Alzheimer’s Disease. Pathology: Research and Practice, 253, Article ID: 155007. [Google Scholar] [CrossRef] [PubMed]
[3] Liu, S., Fan, M., Zheng, Q., et al. (2022) MicroRNAs in Alzheimer’s Disease: Potential Diagnostic Markers and Therapeutic Targets. Biomedicine & Pharmacotherapy, 148, Article ID: 112681. [Google Scholar] [CrossRef] [PubMed]
[4] Zhang, H., Liu, W., Ge, H., et al. (2021) Aberrant Expression of MiR-148a-3p in Alzheimer’s Disease and Its Protective Role against Amyloid-β Induced Neurotoxicity. Neuroscience Letters, 756, Article ID: 135953. [Google Scholar] [CrossRef] [PubMed]
[5] Yuan, J., Wu, Y., Li, L., et al. (2020) MicroRNA-425-5p Promotes Tau Phosphorylation and Cell Apoptosis in Alzheimer’s Disease by Targeting Heat Shock Protein B8. Journal of Neural Transmission, 127, 339-346. [Google Scholar] [CrossRef] [PubMed]
[6] Lewis, B.P., Burge, C.B. and Bartel, D.P. (2005) Conserved Seed Pairing, Often Flanked by Adenosines, Indicates That Thousands of Human Genes Are MicroRNA Targets. Cell, 120, 15-20. [Google Scholar] [CrossRef] [PubMed]
[7] Wong, N. and Wang, X. (2015) MiRDB: An Online Resource for MicroRNA Target Prediction and Functional Annotations. Nucleic Acids Research, 43, D146-D152. [Google Scholar] [CrossRef] [PubMed]
[8] Dennis Jr., G., Sherman, B.T., Hosack, D.A., et al. (2003) DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biology, 4, Article No. P3. [Google Scholar] [CrossRef] [PubMed]
[9] Szklarczyk, D., Franceschini, A., Wyder, S., et al. (2015) STRING V10: Protein-Protein Interaction Networks, Integrated over the Tree of Life. Nucleic Acids Research, 43, D447-D452. [Google Scholar] [CrossRef] [PubMed]
[10] Xia, L., Zhang, F., Li, Y., et al. (2023) A New Perspective on Alzheimer’s Disease: M6A Modification. Frontiers in Genetics, 14, Article 1166831. [Google Scholar] [CrossRef] [PubMed]
[11] Jia, L.H. and Liu, Y.N. (2016) Downregulated Serum MiR-223 Servers as Biomarker in Alzheimer’s Disease. Cell Biochemistry and Function, 34, 233-237. [Google Scholar] [CrossRef] [PubMed]
[12] Liu, Q. and Lei, C. (2021) Neuroprotective Effects of MiR-331-3p through Improved Cell Viability and Inflammatory Marker Expression: Correlation of Serum MiR-331-3p Levels with Diagnosis and Severity of Alzheimer’s Disease. Cell Biochemistry and Function, 144, Article ID: 111187. [Google Scholar] [CrossRef] [PubMed]
[13] Zhang, M., Han, W., Xu, Y., et al. (2021) Serum MiR-128 Serves as a Potential Diagnostic Biomarker for Alzheimer’s Disease. Neuropsychiatric Disease and Treatment, 17, 269-275. [Google Scholar] [CrossRef] 
[14] Wang, R. and Zhang, J. (2020) Clinical Significance of MiR-433 in the Diagnosis of Alzheimer’s Disease and Its Effect on Aβ-Induced Neurotoxicity by Regulating JAK2. Experimental Gerontology, 141, Article ID: 111080. [Google Scholar] [CrossRef] [PubMed]
[15] Kang, Q., Xiang, Y., Li, D., et al. (2017) MiR-124-3p Attenuates Hyperphosphorylation of Tau Protein-Induced Apoptosis via Caveolin-1-PI3K/Akt/GSK3β Pathway in N2a/APP695swe Cells. Oncotarget, 8, 24314-24326. [Google Scholar] [CrossRef] [PubMed]
[16] Hu, G.J., Jiang, X.Y., Du, S.Y., et al. (2024) MiR-107-5p Ameliorates Neurological Damage, Oxidative Stress, and Immune Responses in Mice with Alzheimer’s Disease by Suppressing the Toll-Like Receptor 4 (TLR4)/Nuclear Factor-κB(NF-κB) Pathway. The Kaohsiung Journal of Medical Sciences, 40, 119-130. [Google Scholar] [CrossRef] [PubMed]
[17] Wang, H., Zeng, Z., Yi, R., et al. (2022) MicroRNA-3200-3p Targeting CAMK2A Modulates the Proliferation and Metastasis of Glioma in Vitro. Bioengineered, 13, 7785-7797. [Google Scholar] [CrossRef] [PubMed]
[18] Hui, K., Dong, C., Hu, C., et al. (2024) VEGFR Affects MiR-3200-3p-Mediated Regulatory T Cell Senescence in Tumour-Derived Exosomes in Non-Small Cell Lung Cancer. Functional & Integrative Genomics, 24, Article No. 31. [Google Scholar] [CrossRef] [PubMed]
[19] 冯豆, 张洪, 范月莹, 等. MiR-3200-3p调控Wnt/β-catenin通路影响肝癌细胞的迁移和侵袭[J]. 南昌大学学报(医学版), 2022, 62(2): 14-19. [Google Scholar] [CrossRef] 
[20] Fang, X., Tang, W., Yang, F., et al. (2019) A Comprehensive Analysis of the CaMK2A Gene and Susceptibility to Alzheimer’s Disease in the Han Chinese Population. Frontiers in Aging Neuroscience, 11, Article 84. [Google Scholar] [CrossRef] [PubMed]
[21] Fessel, J. (2023) The Several Ways to Authentically Cure Alzheimer’s Dementia. Ageing Research Reviews, 92, Article ID: 102093. [Google Scholar] [CrossRef] [PubMed]
[22] Wang, Q., Huang, X., Su, Y., et al. (2022) Activation of Wnt/β-Catenin Pathway Mitigates Blood-Brain Barrier Dysfunction in Alzheimer’s Disease. Brain, 145, 4474-4488. [Google Scholar] [CrossRef] [PubMed]
[23] Xia, P., Ma, H., Chen, J., et al. (2023) Differential Expression of Pyroptosis-Related Genes in the Hippocampus of Patients with Alzheimer’s Disease. BMC Medical Genomics, 16, Article No. 56. [Google Scholar] [CrossRef] [PubMed]
[24] Riviere, A., Selak, M., Lantin, D., et al. (2016) Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut. Frontiers in Microbiology, 7, Article 979. [Google Scholar] [CrossRef] [PubMed]
[25] Haran, J.P., Bhattarai, S.K., Foley, S.E., et al. (2019) Alzheimer’s Disease Microbiome Is Associated with Dysregulation of the Anti-Inflammatory P-Glycoprotein Pathway. mBio, 10, e00632-19. [Google Scholar] [CrossRef] 
[26] Van Bergeijk, P., Seneviratne, U., Aparicio-Prat, E., et al. (2019) SRSF1 and PTBP1 Are Trans-Acting Factors That Suppress the Formation of A CD33 Splicing Isoform Linked to Alzheimer’s Disease Risk. Molecular and Cellular Biology, 39, e00568-18. [Google Scholar] [CrossRef] 
[27] Jakubauskiene, E., Vilys, L., Peciuliene, I., et al. (2021) The Role of Hypoxia on Alzheimer’s Disease-Related APP and Tau MRNA Formation. Gene, 766, Article ID: 145146. [Google Scholar] [CrossRef] [PubMed]
[28] Wang, Y.Z., Qian, Y.C., Yang, W.J., et al. (2023) CHD1 Deletion Stabilizes HIF1alpha to Promote Angiogenesis and Glycolysis in Prostate Cancer. Asian Journal of Andrology, 25, 152-157. [Google Scholar] [CrossRef] [PubMed]
[29] Potashkin, J.A., Bottero, V., Santiago, J.A., et al. (2019) Computational Identification of Key Genes That May Regulate Gene Expression Reprogramming in Alzheimer’s Patients. PLOS ONE, 14, e0222921. [Google Scholar] [CrossRef] [PubMed]
[30] Jiang, X. and Chen, D. (2020) LncRNA FAM181A-AS1 Promotes Gliomagenesis by Sponging MiR-129-5p and Upregulating ZRANB2. Aging, 12, 20069-20084. [Google Scholar] [CrossRef] [PubMed]
[31] Cohen, O.S., Weickert, T.W., Hess, J.L., et al. (2016) A Splicing-Regulatory Polymorphism in DRD2 Disrupts ZRANB2 Binding, Impairs Cognitive Functioning and Increases Risk for Schizophrenia in Six Han Chinese Samples. Molecular Psychiatry, 21, 975-982. [Google Scholar] [CrossRef] [PubMed]
[32] Chen, F., Zhang, W., Xu, S., et al. (2023) Discovery and Validation of PURA as a Transcription Target of 20(S)-Protopanaxadiol: Implications for the Treatment of Cognitive Dysfunction. Journal of Ginseng Research, 47, 662-671. [Google Scholar] [CrossRef] [PubMed]
[33] Del Blanco, B., Ninerola, S., Martin-Gonzalez, A.M., et al. (2024) Kdm1a Safeguards the Topological Boundaries of PRC2-Repressed Genes and Prevents Aging-Related Euchromatinization in Neurons. Nature Communications, 15, Article No. 1781. [Google Scholar] [CrossRef] [PubMed]
[34] Karwacki-Neisius, V., Jang, A., Cukuroglu, E., et al. (2024) WNT Signalling Control by KDM5C During Development Affects Cognition. Nature, 627, 594-603. [Google Scholar] [CrossRef] [PubMed]

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