慢性血栓栓塞性肺动脉高压显著相关的微RNA

Analysis of significant microRNA associated with chronic thromboembolic pulmonary hypertension

目的探索与慢性血栓栓塞性肺动脉高压（CTEPH）显著相关的微RNA（miR）。方法通过整合Affymetrix miR芯片数据以及从高通量基因表达数据库（GEO）公共数据库上下载的GSE56914数据。两套芯片数据均来自于CTEPH患者和匹配的健康受试者的外周血标本。筛选两套数据中的差异表达miR，搜索这些miR的靶基因。并对这些miR进行功能富集分析。最后构建了包括miR、靶基因和通路的疾病关联网络。结果筛选出hsa-miR-885-5p、hsa-miR-501-5p、hsa-miR-615-3p、hsa-miR-610和hsa-miR-346等5个对该疾病起重要作用的miR，而且这5个miR在两个数据集中均为显著下调。hsa．miR-885-5p和hsa-miR-501-5p显著参与细胞周期通路，hsa-miR-615-3p显著参与细胞因子-细胞因子受体相互作用，轴突导向，黏着斑和细胞周期通路，hsa-miR-610显著参与黏着斑通路，hsa-miR-346显著参与细胞因子-细胞因子受体相互作用，轴突导向和黏着斑通路。结论hsa-miR-885-5p、hsa-miR-501-5p、hsa-miR-615-3p、hsa-miR-610和hsa-miR-346是与CTEPH显著相关的miR。

Objective To find key microRNA （miR） associated with chronic thromboembolic pulmonary hypertension （CTEPH）. Methods Affymetrix miR microarray data and GSE56914 data downloaded from GEO database （http ：//www. ncbi. nlm. nih. gov/geo/） were obtained and integrated. The microarray data were obtained from peripheral blood samples of CTEPH patients and the matched control. Differentially expressed miRs were screened. Target genes of these miRs were searched. Then, functional enrichment analyses for these miRs were performed. After that, disease network including miRs, target genes and pathways was constructed. Resnlts Five important miRs including hsa-miR-885-5p, hsa-miR-501-5p, hsa-miR-615-3p, hsa-miR-610, and hsa-miR-346 were identified. Furthermore, hsa-miR-885-5p and hsa- miR-501-5p were significantly enriched in cell cycle pathway. Hsa-miR-615-3p was involved in cytokine- cytokine receptor interaction, axon guidance, focal adhesion and cell cycle pathway. Hsa-miR-610 was significantly enriched in focal adhesion pathway, and hsa-miR-346 was involved in eytokine-eytokine receptor interaction, axon guidance, and focal adhesion pathway. Conclusions Hsa-miR-885-5p, hsa-miR-501-5p, hsa-miR-615-3p, hsa-miR-610 and hsa-miR-346 are imnortant miRs for the develooment of CTEPH.