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综合生物信息学分析揭示 miR-200b-3p 在子宫内膜异位症中的功能和调控网络。

Integrated Bioinformatics Analysis Reveals Function and Regulatory Network of miR-200b-3p in Endometriosis.

机构信息

Biomedical Engineering Research Center, Kunming Medical University, Kunming 650500, China.

School of Rehabilitation, Kunming Medical University, Kunming 650500, China.

出版信息

Biomed Res Int. 2020 Jul 29;2020:3962953. doi: 10.1155/2020/3962953. eCollection 2020.

Abstract

OBJECTIVE

MicroRNAs play vital roles in the development of endometriosis. It is reported that miR-200b-3p is downregulated in endometriosis, although its mechanisms in this disease remain still unclear. Therefore, the purpose of this study was to explore the function and potential regulatory network of miR-200b-3p in endometriosis through database analysis.

METHODS

The endometriosis gene expression profiles were downloaded from the GEO database to screen differentially expressed genes (DEGs). The predicted and validated target genes of miR-200b-3p were obtained from miRWalk and miRTarBase database. Then, a comparison was performed between miR-200b-3p target genes and DEGs. GO enrichment and KEGG pathway analysis of the target genes was performed using clusterProfiler package. STRING was used to predict the protein-protein interaction among the proteins encoded by the target genes. Then, TransmiR, LncBase, StarBase, PROMO, and AnimalTFDB were employed to identify interactive transcription factors and lncRNAs of miR-200b-3p.

RESULTS

miR-200b-3p was associated with the transcription factors DNMT1, EZH2, HNF1B, JUN, MYB, ZEB1, and ZEB2 during the pathogenesis of endometriosis. The downstream 110 target genes were involved in the biological processes of positive regulation of MAPK cascade, muscle cell proliferation, organ growth, vasculogenesis, and axon development. KEGG analysis revealed that the main pathways related to miR-200b-3p were microRNAs in cancer, PI3K-Akt signaling pathway, colorectal cancer, and tight junction. In addition, four lncRNAs such as MALAT1, NEAT1, SNHG22, and XIST interacted with miR-200b-3p and were associated with transcription factors FOXP3 and YY1.

CONCLUSION

The predicted target genes and molecular regulatory network of miR-200b-3p in endometriosis not only revealed its biological function but also provided a valuable guideline for further research.

摘要

目的

微小 RNA 在子宫内膜异位症的发生发展中发挥着重要作用。有报道称,miR-200b-3p 在子宫内膜异位症中表达下调,但其在该疾病中的作用机制尚不清楚。因此,本研究通过数据库分析旨在探讨 miR-200b-3p 在子宫内膜异位症中的功能及其潜在的调控网络。

方法

从 GEO 数据库下载子宫内膜异位症基因表达谱,筛选差异表达基因(DEGs)。从 miRWalk 和 miRTarBase 数据库中获得 miR-200b-3p 的预测和验证靶基因。然后,比较 miR-200b-3p 靶基因与 DEGs。使用 clusterProfiler 软件包对靶基因进行 GO 富集和 KEGG 通路分析。使用 STRING 预测靶基因编码蛋白之间的蛋白质-蛋白质相互作用。然后,利用 TransmiR、LncBase、StarBase、PROMO 和 AnimalTFDB 识别 miR-200b-3p 的互作转录因子和 lncRNA。

结果

miR-200b-3p 在子宫内膜异位症的发病机制中与转录因子 DNMT1、EZH2、HNF1B、JUN、MYB、ZEB1 和 ZEB2 相关。下游的 110 个靶基因参与了 MAPK 级联的正调控、肌肉细胞增殖、器官生长、血管生成和轴突发育等生物学过程。KEGG 分析显示,与 miR-200b-3p 相关的主要途径包括癌症中的 microRNAs、PI3K-Akt 信号通路、结直肠癌和紧密连接。此外,MALAT1、NEAT1、SNHG22 和 XIST 等 4 个 lncRNA 与 miR-200b-3p 相互作用,并与转录因子 FOXP3 和 YY1 相关。

结论

预测的 miR-200b-3p 在子宫内膜异位症中的靶基因及其分子调控网络不仅揭示了其生物学功能,而且为进一步研究提供了有价值的指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74c3/7414375/9fce1a040d64/BMRI2020-3962953.001.jpg

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