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| 基因差异表达谱及WGCNA构建骨质疏松症miRNA-mRNA调控网络 |
| Construction of osteoporosis related miRNA-mRNA regulatory network via gene differentially expressed profile and WGCNA analysis |
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| DOI：10.3969/j.issn.1006-7108.2022.06.002 |
| 中文关键词: 骨质疏松症 加权基因共表达网络分析 微型核糖核酸 调控网络 |
| 英文关键词:osteoporosis WGCNA miRNA regulatory network |
| 基金项目:国家自然科学资金（81973886）；广州中医药大学学科研究重点项目（XK2019028） |
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| 中文摘要: |
| 目的 通过基因差异表达谱及加权基因共表达网络分析（WGCNA）方法构建并分析骨质疏松症相关的miRNA-mRNA调控网络，全面阐释骨质疏松症的发病机制。方法 首先在GEO数据库中获取微阵列数据集，进行差异分析及WGCNA分析，获取差异miRNA和临床相关性最高的模块基因，并取交集。预测潜在上游转录因子及下游靶基因。同时，获取差异表达mRNA并与预测靶基因取交集得到关键miRNA目标靶基因，进行目标靶基因GO和KEGG通路富集分析。通过String获取目标靶基因PPI关系文件，然后通过Cytoscape构建并分析miRNA-mRNA网络。结果 共得到6个与骨质疏松症疾病相关的关键miRNA,其中2个差异性上调、4个差异性下调，其主要转录因子为SP4、LHX3、NFIC、MYC和VSX2。通过将预测得到的关键miRNA靶基因和差异表达mRNA取交集，获得目标靶基因52个。GO和KEGG富集分析显示目标靶基因涉及多个生物学进程及通路，其中趋化因子信号通路、P53信号通路值得关注。结论 骨质疏松症miRNA-mRNA表达是通过多途径、多靶点进行调控的，hsa-mir-4500、CDKN1A、MAP2K7组成其核心调控网络。本研究为深入探讨骨质疏松症的分子机制提供了新的思路，发现了新的潜在靶点，对阐明其发病机制及防治药物的开发具有重要的指导意义。 |
| 英文摘要: |
| Objective To construct and analyze the miRNA-mRNA regulatory network related to osteoporosis via gene differentially expressed profile and WGCNA method. Methods Identified differentially expressed miRNA profiles, and miRNAs from clinical related module was obtained by WGCNA method. The overlap of module genes and differentially expressed miRNAs were considered as key miRNAs. Subsequently predicted mRNAs and upstream transcription factors were acquired. Then intersected mRNAs of predicted targets and differentially expressed mRNAs were identified, based on which GO and KEGG enrichment analysis were performed. Finally, regulatory miRNA-mRNA network, taking PPI relationship into consideration, was constructed and analyzed by Cytoscape. Results A total of 6 differentially expressed and clinical related miRNAs were identified as key miRNAs, in which 2 were upregulated and 4 were downregulated. SP4, LHX3, NFIC, MYC and VSX2 were considered as key transcription factors of key miRNAs. GO and KEGG analysis indicated multiple processes and pathways were involved, among which Chemokine signaling pathway and p53 signaling pathway were worthy of attention. Conclusion The expression of miRNA-mRNA in osteoporosis is regulated through multiple ways and multiple targets, and hsa-miR-4500, CDKN1A and MAP2K7 are the core regulatory networks. This study provides a new insight into the study of the molecular mechanism and uncovering of new potential targets of osteoporosis, which has important guiding significance for elucidating the pathogenesis of osteoporosis and the development of potential drugs. |
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