加权基因共表达网络筛选HIV-1转录过程中关键circRNA  

Screen the key circ RNAs during HIV transcription by weighted gene co-expression network

作　　者：杜娟[1] 林元龙 陈晓红[3] 李锦 梁晗[5] 张铮 王福祥 邵冰[1] 宋波[3] DU Juan;LIN Yuanlong;CHEN Xiaohong;LI Jin;LIANG Han;ZHANG Zheng;WANG Fuxiang;SHAO Bing;SONG Bo(School of Pharmacy,Jilin Medical College,Jilin 132013,Jilin,China;Shenzhen Third People's Hospital,Shenzhen 518112,Guangdong;The Fourth Afiliated Hospital of Harbin Medical University,Harbin 150001,Heilongjiang;Changchun Infectious Disease Hospital,Changchun 130123,Jilin;Jilin Infectious Disease Hospital,Jilin 132002,Jilin;Shenzhen Longgang People's Hospital,Shenzhen 518100,Guangdong)

机构地区：[1]吉林医药学院,吉林吉林132013 [2]深圳市第三人民医院,广东深圳518112 [3]哈尔滨医科大学附属第四医院,哈尔滨150001 [4]长春市传染病医院,长春130123 [5]吉林市传染病医院,吉林吉林132002 [6]深圳市龙岗人民医院,广东深圳518100

出　　处：《中国艾滋病性病》2022年第8期888-894,共7页Chinese Journal of Aids & STD

基　　金：国家自然科学基金(81602899,81971915);吉林省科技发展计划优秀青年人才基金项目(20180520107 JH);吉林省卫生健康青年科技骨干培养计划(2019Q034);吉林省教育厅“十三五”科学技术项目(JJKH20200464KJ);国家科技重大专项(2017ZX10202102)。

摘　　要：目的筛选参与HIV-1转录过程中可能起关键生物学作用的环状RNA(circRNA)。方法采集HIV-1感染者和健康人的血液样本,分离外周血单个核细胞(PBMCs),采用PCR荧光探针法对PBMCs内HIV-1总DNA和RNA进行定量检测,同时对样本的基因表达谱进行检测。采用加权基因共表达网络法(WGCNA)构建含有circRNA和mRNA的共表达网络模块,对模块内的circRNA可能参与的生物学功能进行分析,并筛选可能起关键作用的circRNA。结果基于WGCNA共构建出17个功能性模块,筛选出与HIV-1转录相关性最强的darkred和darkturquoise模块。在darkred模块中筛选出2个circRNA:hsa_circ_0013704和hsa_circ_0059500,这两个circRNA可能通过与NAMPT、CMTM2蛋白相互作用发挥其蛋白海绵功能,从而解除它们对HIV-1 Tat蛋白的抑制作用,进而促进HIV-1的基因转录激活。结论hsa_circ_0013704和hsa_circ_0059500在HIV-1转录过程中可能具有重要作用,但其生物学机制有待进一步实验证实。Objective To screen circRNAs that may play key biological roles in HIV gene transcription.Methods Blood samples from HIV-1 infected and healthy people were collected.PBMCs cells were isolated and the total HIV-1DNA and RNA in PBMCs cells were quantitatively detected by PCR fluorescent probe method.Meanwhile,the gene expression profiles of the samples were detected.The weighted gene co-expression network method(WGCNA)was used to construct a co-expression network module containing circRNA and mRNA.The biological functions of circRNAs in the modules were analyzed and the circRNAs that may play a key role were screened.Results A total of 17 functional modules were constructed based on WGCNA and the darkred and darkturquoise modules with the strongest correlation with HIV gene transcription were screened.Two circRNAs were screened in the darkred module:hsa_circ_0013704 and hsa_circ_0059500.These two circRNAs may play their protein sponge function by interacting with NAMPT and CMTM2 proteins,thereby releasing their inhibitory effect on HIV-1 tat protein,and exerting their biological functions of promoting HIV gene transcriptional activation.Conclusions hsa_circ_0013704 and hsa_circ_0059500 may play important roles in HIV-1 gene transcription,but the biological mechanism remains to be confirmed by further experiments.

关 键 词：1型艾滋病病毒 加权基因共表达网络 环状核糖核酸 转录激活 

分 类 号：R512.91[医药卫生—内科学] R373.9[医药卫生—临床医学]