摘要
目的探索结核分枝杆菌抵抗人或小鼠巨噬细胞自噬机制的关键miRNAs及circRNAs,为寻找新型结核诊断标志物及治疗靶点提供思路。方法筛选出结核分枝杆菌诱导细胞差异表达的自噬相关基因;制作蛋白交互图并文献挖掘筛选关键自噬基因;多数据库综合预测相应的miRNA,制作自噬基因mRNA-miRNAs交联图并筛选关键miRNA;制作miRNAs-circRNAs相互作用图并筛选关键circRNA。结果筛选出18种结核感染后差异表达的自噬相关基因,并在此基础上预测16种自噬关键基因;筛选出4种通过靶向自噬mRNA参与自噬调控的关键miRNA分子(miR-17-5p,miR-20a-5p,miR-30a-5p,miR-33-5p);针对4种miRNA筛选出6种与其密切相关的circRNA分子,并预测hsa-circRNA2908和hsa-circRNA6439是影响结核抗自噬关键circRNA分子。结论 miR-miR-17-5p,miR-20a-5p,miR-30a-5p,miR-33-5p及其上游共同调控分子hsa-circRNA2908和hsa-circRNA6439可能是潜在的诊断标志物和疾病治疗靶点。
We explored the pivotal miRNAs and circRNAs which can affect the Mycobacterium tuberculosis(MTB)resistance to the human or mice macrophage autophagy,to provide the new way to find the novel tuberculosis diagnosis biomarker and therapeutic target meanwhile.We screened and filtrated the differentiated expressed autophagy related genes regulated by MTB in infected macrophage and selected the pivotal autophagy genes from the protein-protein interactions diagram and literature mining.We also integrated forecasting the relevant miRNA with that through multiple predicting databases,create the autophagy gene mRNA-miRNAs interaction diagram and selected the pivotal miRNA,verifying them by literature or experiments.Then we created miRNAs-circRNAs interactions diagram and selected the pivotal circRNA likewise.Of 18 autophagy related genes with differentiated expression in MTB infected cells were filtrated,and 16 crucial autophagy genes were predicted in the basis.Moreover four pivotal miRNAs(miR-17-5p,miR-20a-5p,miR-30a-5p,miR-33-5p)were selected which regulate autophagy by targeting mRNA of autophagy genes.In addition,six relevant potential circRNAs were selected by virtue of analysis of the connection with that four mRNAs,and speculating that has-circRNA2908 and has-circRNA6439 would be the pivotal circRNA to impair MTB resistance to cell autophagy.MiR-17-5p,miR-20a-5p,miR-30a-5p,miR-33-5p and their common upstream regulating molecules,has-circRNA2908 and has-circRNA6439 may be potential diagnosis biomarker and therapeutic target of disease.
作者
张益源
罗嘉婧
伊正君
付玉荣
ZHANG Yi-yuan;LUO Jia-jing;YI Zheng-jun;FU Yu-rong(College Clinical Medicine,Weifang Medical University,Weifang 261053,China;Department of Clinical Laboratory,Weifang Medical University,Weifang 261053,China)
出处
《中国人兽共患病学报》
CAS
CSCD
北大核心
2018年第10期888-894,907,共8页
Chinese Journal of Zoonoses
基金
国家自然科学基金(No.81470001)
山东省自然科学基金(No.ZR2016HM09)联合资助。
