中国药理学通报2016，Vol.32Issue(9)：1294-1300,7.DOI:10.3969/j.issn.1001-1978.2016.09.021
肺动脉高压时肺血管内皮间质转化相关miRNAs网络调控的生物信息学分析
MicroRNAs integrates pathogenic signaling to control endothelial-mesenchymal transition in pulmonary hypertension：results of a network bioinformatic approach
摘要
Abstract
Aim To explore micro RNAs-integrated pathogenic signaling to control endothelial-mesenchy-mal transition ( EndMT ) in pulmonary hypertension ( PH) by a network bioinformatic approach. Methods Literature-mining method was used to find PH-relat-ed genes and EndMT/EMT-related miRNAs. Bioinfor-matic prediction approach ( DIANA3 , Miranda4 , PicT-ar5 , TargetScan6 , miRDB7 and microT-CDS8 ) was used for miRNA target prediction. Hypergeometric a-nalysis was used to predict miRNAs related to EndMT in PH. The analysis of interactions between PH-rele-vant genes( PH network) was performed with the use of Biological General Repository for Interaction Datasets ( BioGRID ) . These miRNAs were ranked with the highest probability of substantial overlap among their gene targets in the PH-network, the relationship be-tween their targets and the PH functional categories which include hypoxia, inflammation, and transforming growth factor/BMP signaling. Then, the part of results was validated by animal experiment. Lastly the miR-NA-Target network was built using Cytocape 3 . Results List of 230 genes was compiled that were directly im-plicated in the development of PH and 189 miRNAs were related to EndMT in PH. Among 189 miRNAs, only 22 microRNAs(miR-let-7 family, miR-124, miR-130 family, miR-135, miR-144, miR-149, miR-155, miR-16-1, miR-17, miR-181 family, miR-182, miR-200 family, miR-204, miR-205, miR-21, miR-224, miR-27, miR-29 family, miR-301a, miR-31, miR-361 and miR-375) were related to hypoxia, inflamma-tion, and transforming growth factor/BMP signaling. Among these miRNAs, the levels of let-7g, miR-21, miR-124 and miR-130 family were significantly changed in the pulmonary artery in hypoxia-induced PH rats. Conclusions Among numerous miRNAs,22 of which may be involved in hypoxia, inflammation, and transforming growth factor/BMP signaling and re-lated to EndMT in PH by network bioinformatic ap-proach, which provides a theoretical basis for further investigation of EndMT in PH.关键词
肺动脉高压/miRNAs/内皮间质转化/网络调控/生物信息学/网络药理/相互作用Key words
pulmonary hypertension/miRNAs/End-MT/network regulation/bioinformatics/network phar-macology/interaction分类
医药卫生引用本文复制引用
张卫芳,熊爱珍,吴卫华,祝田田,邹小舟,刘汀,胡长平..肺动脉高压时肺血管内皮间质转化相关miRNAs网络调控的生物信息学分析[J].中国药理学通报,2016,32(9):1294-1300,7.基金项目
国家自然科学基金资助项目( No 81273512,81473209,91439105,81460010) （ No 81273512,81473209,91439105,81460010）
江西省科技厅青年科学基金( No 20142BAB215035) （ No 20142BAB215035）
南昌大学第二附属医院院内课题( No 20142YNQN12018) （ No 20142YNQN12018）
