Prediction of target genes for miR-140-5p in pulmonary arterial hypertension using bioinformatics methods.
Prediction of target genes for miR-140-5p in pulmonary arterial hypertension using bioinformatics methods.
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利用生物信息学方法预测肺动脉高压中miR-140-5p的靶基因
DOI：
10.1002/2211-5463.12322
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发表时间：
2017-12
期刊：
影响因子：
2.6
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
Li F;Shi W;Wan Y;Wang Q;Feng W;Yan X;Wang J;Chai L;Zhang Q;Li M
已知在大鼠肺动脉高压(PAH)患者和野百合碱诱导的PAH模型中，microRNA(MiR)-140-5p的表达都降低。通过生物信息学分析鉴定miR-140-5p的靶基因，可能揭示PAH中新的途径和联系。本研究旨在探索miR-140-5p调控的下游靶基因及相关信号通路，为进一步研究miR-140-5p在PAH中的作用提供理论依据。在分析中预测了miR-140-5p的多个下游靶基因和上游转录因子。基因本体论(GO)分析表明miR-140-5p下游靶基因在生物调节、信号转导、对化学刺激的应答、干细胞增殖、细胞表面受体信号通路等多个生物学过程中均有丰富。京都基因和基因组百科全书(KEGG)途径分析发现，下游靶基因主要位于Notch、转化生长因子-β、PI3K/Akt和Hippo信号通路。根据TF-miRNA-mRNA网络，miR-140-5p的重要下游靶基因是PPI、转化生长因子-β1、Smad4、JAG1、ADAM10、FGF9、PDGFRA、VEGFA、LAMC1、TLR4和CREB。在深入查阅已发表的文献后，我们发现miR-140-5p在不同的组织或细胞中确实抑制了23个靶基因和7个信号通路；这些验证的靶点大多与我们目前的预测一致。其他预测的靶点还需要在体内和体外进一步验证。
The expression of microRNA (miR)‐140‐5p is known to be reduced in both pulmonary arterial hypertension (PAH) patients and monocrotaline‐induced PAH models in rat. Identification of target genes for miR‐140‐5p with bioinformatics analysis may reveal new pathways and connections in PAH. This study aimed to explore downstream target genes and relevant signaling pathways regulated by miR‐140‐5p to provide theoretical evidences for further researches on role of miR‐140‐5p in PAH. Multiple downstream target genes and upstream transcription factors (TFs) of miR‐140‐5p were predicted in the analysis. Gene ontology (GO) enrichment analysis indicated that downstream target genes of miR‐140‐5p were enriched in many biological processes, such as biological regulation, signal transduction, response to chemical stimulus, stem cell proliferation, cell surface receptor signaling pathways. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis found that downstream target genes were mainly located in Notch, TGF‐beta, PI3K/Akt, and Hippo signaling pathway. According to TF–miRNA–mRNA network, the important downstream target genes of miR‐140‐5p were PPI, TGF‐betaR1, smad4, JAG1, ADAM10, FGF9, PDGFRA, VEGFA, LAMC1, TLR4, and CREB. After thoroughly reviewing published literature, we found that 23 target genes and seven signaling pathways were truly inhibited by miR‐140‐5p in various tissues or cells; most of these verified targets were in accordance with our present prediction. Other predicted targets still need further verification in vivo and in vitro.
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影响因子：
3
作者：
Garat CV;Crossno JT Jr;Sullivan TM;Reusch JE;Klemm DJ
通讯作者：
Klemm DJ
影响因子：
3.1
作者：
Higasa K;Ogawa A;Terao C;Shimizu M;Kosugi S;Yamada R;Date H;Matsubara H;Matsuda F
通讯作者：
Matsuda F
影响因子：
7.4
作者：
Chuang, Jih-Ing;Huang, Jui-Yen;Ching, Cheng-Hsin
通讯作者：
Ching, Cheng-Hsin
影响因子：
15.9
作者：
Rothman, Alexander M. K.;Arnold, Nadine D.;Lawrie, Allan
通讯作者：
Lawrie, Allan
Notch3 的激活通过 Hes1/p27Kip1 信号通路促进肺动脉平滑肌细胞增殖。
影响因子：
2.6
作者：
Song Y;Zhang Y;Jiang H;Zhu Y;Liu L;Feng W;Yang L;Wang Y;Li M
通讯作者：
Li M