MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-c

• 作 者: Huashan Ye Haibo Jia Jun Sun Zhichao Chen An-Yuan Guo Xiaowen Liu Meng Lv Yuliang Wu Shuzhen Kuang Jing Gong Ping Yuan Zhaodong Zhong Qiubai Li
• 机 构: Hubei Bioinformatics and Molecular Imaging Key Laboratory, Department of Systems Biology,College of
• 出 处: 第一届国际转化医学信息学会议
• 发表日期: 2012年7期

　　T-cell acute lymphoblastic leukemia (T-ALL) is anaggressive hematological malignancy.The under-standing of its gene expression regulation and mo-lecular mechanisms still remains elusive.Started from experimentally verified T-ALL-related miRNAs and genes, we obtained 120 feed-forward loops (FFLs) among T-ALL-related genes, miRNAs and TFs through combining target prediction.Afterwards, a T-ALL miRNA and TF co-regulatory network was constructed, and its significance was tested by statistical methods.Four miRNAs in the miR-17-92 cluster and four important genes (CYLD, HOXA9, BCL2L11 and RUNX1) were found as hubs in the network.Particularly, we found that miR-19 was highly expressed in T-ALL patients and cell lines.Ectopic expression of miR-19 represses CYLD expression,while miR-19 inhibitor treatment induces CYLD protein expression and decreases NF-iB expression in the downstream signaling pathway.Thus, miR-19, CYLD and NF-iB form a regulatory FFL, which provides new clues for sus-tained activation of NF-iB in T-ALL.Taken together, we provided the first miRNA-TF co-regulatory network in T-ALL and proposed a model to demon-strate the roles of miR-19 and CYLD in the T-cell leukemogenesis.This study may provide potential therapeutic targets for T-ALL and shed light on combining bioinformatics with experiments in the research of complex diseases.