基于生物信息学分析长非编码RNA在变应性鼻炎中的机制

Based on bioinformatics to analyze the mechanism of long non-coding RNA in allergic rhinitis

摘要:

目的：识别变应性鼻炎（Allergic rhinitis，AR）疾病进展的差异表达基因，探索其竞争性内源RNA（competing endogenous RNA，ceRNA）网络调控机制，并筛选潜在的治疗靶点。 方法：检索GEO数据库，下载AR的微阵列芯片GSE46171。借助R语言等软件分析得到差异的长非编码RNA(long non-coding RNA，lncRNA)与信使RNA（messenger RNA，mRNA），并通过公共数据库预测与差异lncRNA互作的微小RNA(microRNA，miRNA)及其调控的mRNA，再与差异mRNA取交集，整合得到lncRNA-miRNA-mRNA关系，构建ceRNA网络。随后采用STRING数据库和cytoscape软件筛选关键基因，利用DAVID数据库分析关键基因的基因功能与相关通路，挖掘关键ceRNA网络。 结果：①与正常鼻黏膜组织对比，AR患者鼻黏膜组织35个lncRNA和2071个mRNA存在差异表达；②筛选出CREB1、PPARG、ETS1、IRF4、JAK2共5个关键基因；③关键基因所富集的功能包括髓细胞分化、DNA结合的正调控等生物学过程，涉及Longevity、AMPK、IL?17等信号通路；④6种miRNA（miR-27a-3p、miR-125a-5p、miR-135a-5p、miR-125b-5p、miR-17-5p、miR-20b-5p）可能在导致AR发生发展过程中发挥关键作用。 结论：通过对变应性鼻炎相关lncRNA介导的ceRNA网络进行分析，识别出潜在的治疗靶点及信号通路，为进一步阐明其发病机制，并为后续的实验研究提供参考依据。

Abstract:

Objective To identify the differentially expressed genes of allergic rhinitis (AR) disease progression, to explore the regulatory mechanism of its competing endogenous RNA (ceRNA) network, and to screen potential therapeutic targets. Methods Search the GEO database and download AR's microarray chip GSE46171. Using R language and other software to analyze the differential long non-coding RNA (lncRNA) and messenger RNA (mRNA), and predict the microRNA (miRNA) that interacts with the differential lncRNA through the public database and the mRNAs it regulates, and then intersect with the differential mRNAs to obtain the lncRNA-miRNA-mRNA relationship to construct a ceRNA network. Then, the STRING database and cytoscape software were used to screen key genes, and the DAVID database was used to analyze the gene functions and related pathways of key genes, and mine key ceRNA networks. Result ①Compared with normal nasal mucosa tissue, 35 lncRNAs and 2071 mRNAs were differentially expressed in nasal mucosa tissue of AR patients; ②5 key genes were screened out, including CREB1, PPARG, ETS1, IRF4, and JAK2; ③The enriched functions of key genes include Biological processes such as myeloid differentiation and positive regulation of DNA binding involve signaling pathways such as Longevity, AMPK, and IL-17; ④ 6 miRNAs (miR-27a-3p, miR-125a-5p, miR-135a-5p, miR- 125b-5p, miR-17-5p, miR-20b-5p) may play a key role in the development of AR. Conclusion Through the analysis of the ceRNA network mediated by lncRNA related to allergic rhinitis, potential therapeutic targets and signal pathways are identified, which can further clarify its pathogenesis and provide a reference for subsequent experimental research.