矽肺大鼠肺组织差异表达环状RNA的筛选及其生物学功能和调控通路分析  

Screening of differentially expressed circular RNAs in lung tissues of silicotic rats and their related biological function and metabolic pathways

作　　者：徐安琪 张玮 张志虎 张放 杨治峰 XU Anqi;ZHANG Wei;ZHANG Zhihu;ZHANG Fang;YANG Zhifeng(Shandong Academy of Occupational Health and Occupational Medicine,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan 250000,China;不详)

机构地区：[1]山东第一医科大学(山东省医学科学院)山东省职业卫生与职业病防治研究院检测评价室,济南250000

出　　处：《山东医药》2022年第35期44-47,共4页Shandong Medical Journal

基　　金：山东省济南市科学技术发展计划第五批项目(201805071)。

摘　　要：目的筛选矽肺大鼠肺组织中的差异表达环状RNA(circRNA),并分析其生物学功能、相关调控通路。方法将20只SPF级Wistar雄性大鼠随机分成模型组和对照组,每组10只,分别采用非暴露法气管内一次性灌注SiO粉尘悬液、灭菌生理盐水各1 mL。两组分组处理30 d,处死后取肺组织,采用高通量circRNA芯片技术筛选两组大鼠肺组织差异表达的circRNA,使用基因本体论(GO)功能与京都基因与基因组百科全书(KEGG)通路富集分析差异表达circRNA的生物学功能及相关通路。结果共筛选出两组大鼠肺组织差异表达circRNA 1129个,其中表达上调的circRNA 293个,表达下调的circRNA 836个。GO功能分析结果显示:分子功能层面,差异表达的circRNA主要影响蛋白质结合蛋白、离子结合、蛋白质的催化活性、蛋白激酶活性;细胞组成层面,差异表达的circRNA主要影响细胞连接、突触、细胞内膜结合、细胞器、细胞内细胞器;生物学过程层面,差异表达的circRNA主要影响阴离子结合、ATP结合、磷酸转移酶活性、蛋白激酶活性。KEGG信号通路分析结果显示,矽肺大鼠肺组织差异表达的circRNA主要与癌症、环磷酸鸟苷—蛋白激酶G(cGMP)—蛋白激酶G(PKG)信号通路、酪氨酸激酶抑制剂耐药性、血管平滑肌收缩、表皮生长因子受体(EGFR)信号通路、钙离子信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、甲状旁腺激素的合成与分泌、谷氨酸能突触等通路相关。结论矽肺大鼠肺组织差异表达circRNA 1129个,其中表达上调的circRNA 293个、表达下调的circRNA 836个,主要影响蛋白质结合蛋白、离子结合等分子功能,细胞连接、突触等细胞组成,阴离子结合、ATP结合等生物学过程,并涉及调控MAPK、EGFR、癌症和钙离子信号通路等。Objective To screen the differentially expressed circular RNAs(circ RNAs)in the lung tissues of silicosis rats,and to analyze their biological function and related metabolic pathways.Methods Twenty SPF Wistar male rats were randomly divided into the model group and control group,with 10 rats in each group.One-time intratracheal infusion of SiOdust suspension and 1 m L sterile saline were used,respectively.The two groups were treated for 30 days,and the lung tissues were taken after being killed.The high-throughput circ RNA chip technology was used to screen the differentially expressed circ RNAs in the lung tissues of the two groups,and the biological functions and related pathways of the differentially expressed circ RNAs were analyzed by gene ontology(GO)function and pathway enrichment database(KEGG).Results A total of 1129 differentially expressed circ RNAs in lung tissues of two groups were screened out,including 293 up-regulated circ RNAs and 836 down-regulated circ RNAs.The results of GO functional analysis showed that:at the molecular functional level,differentially expressed circ RNAs mainly affected protein binding protein,ion binding,catalytic activity of protein and protein kinase activity;at the level of cell composition,differentially expressed circ RNAs mainly affected cell junctions,synapses,intracellular membrane binding,organelles and intracellular organelles;at the level of biological process,differentially expressed circ RNAs mainly affected anion binding,ATP binding,phosphotransferase activity and protein kinase activity.The results of KEGG signal pathway analysis showed that circ RNAs differentially expressed in the lung tissues of silicotic rats were mainly related to cancer,CGMP-PKG signal pathway,tyrosine kinase inhibitor resistance,vascular smooth muscle contraction,epidermal growth factor receptor(EGFR)signal pathway,calcium signal pathway,MAPK signal pathway,parathyroid hormone synthesis and secretion,glutamate synapse and other pathways.Conclusion s There are 1129 differentially expres

关 键 词：环状RNA 矽肺 蛋白质结合蛋白 离子结合 表皮生长因子受体信号通路 

分 类 号：R135[医药卫生—劳动卫生]