近日,国际期刊《核酸研究》Nucleic Acids Research上刊登了华中科技大学生命科学与技术学院郭安源课题组的研究成果,研究者报告了关于急性T淋巴细胞白血病中miRNA和转录因子共调控网络的生物信息学研究最新成果,并在此基础上与同济医学院教授孙军和协和医院血液科教授陈智超合作,对其中的核心调控模块进行了实验验证。
据了解,急性T淋巴细胞白血病(T-ALL)是一种恶性血液疾病,由未分化或分化很差的淋巴细胞在造血组织(特别是骨髓、脾脏和淋巴结)无限增殖所致,多发于儿童和青少年。尽管近年来多药联合、大剂量化疗等治疗手段不断改进,以及各类造血干细胞移植得到应用和推广,但是其治疗效果和预后比更常见的B细胞系淋巴细胞白血病仍然要差很多。目前,关于急性T淋巴细胞白血病的具体分子机理和调控机理还不清楚。
郭安源课题组以miRNA和转录因子的共调控角度为切入点,运用生物信息学方法,预测miRNA和转录因子与疾病基因之间形成的共调控前馈环模块,并由此构建共调控网络。通过深入分析该调控网络,研究人员获得了其中的核心miRNA和基因,并进一步对其中核心基因miR-19与CYLD在T-ALL中的分子机理进行了研究,首次揭示了miR-19抑制CYLD蛋白的产生,继而激活下游的NFKB信号通路,导致T淋巴细胞增殖失控。
该研究成果从系统网络水平上研究了急性T淋巴细胞白血病的发病机理和调控过程,为其诊断和治疗提供了理论依据,同时为复杂疾病的研究提供了计算和实验交叉的新思路和方法。
据悉,郭安源主要从事生物信息学和系统生物学在复杂疾病中的研究,包括数据整合、数据库构建、miRNA调控、比较基因组学和二代测序数据的分析研究等。(生物谷Bioon.com)
doi:10.1093/nar/gkr965
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AnimalTFDB: a comprehensive animal transcription factor database
Hong-Mei Zhang1, Hu Chen1, Wei Liu1, Hui Liu1, Jing Gong1, Huili Wang2 and An-Yuan Guo1,*
Transcription factors (TFs) are proteins that bind to specific DNA sequences, thereby playing crucial roles in gene-expression regulation through controlling the transcription of genetic information from DNA to RNA. Transcription cofactors and chromatin remodeling factors are also essential in the gene transcriptional regulation. Identifying and annotating all the TFs are primary and crucial steps for illustrating their functions and understanding the transcriptional regulation. In this study, based on manual literature reviews, we collected and curated 72 TF families for animals, which is currently the most complete list of TF families in animals. Then, we systematically characterized all the TFs in 50 animal species and constructed a comprehensive animal TF database, AnimalTFDB. To better serve the community, we provided detailed annotations for each TF, including basic information, gene structure, functional domain, 3D structure hit, Gene Ontology, pathway, protein–protein interaction, paralogs, orthologs, potential TF-binding sites and targets. In addition, we collected and annotated transcription cofactors and chromatin remodeling factors. AnimalTFDB has a user-friendly web interface with multiple browse and search functions, as well as data downloading. It is freely available at http://www.bioguo.org/AnimalTFDB/.