结节性硬化症相关肾血管平滑肌脂肪瘤的circRNA表达谱及ceRNA调控网络的构建  

Expression profile of circRNA and construction of ceRNA regulatory network in tuberous sclerosis related renal angiomyolipoma(TSC-RAML)

作　　者：王站 郭浩[1] 蔡燚 赵扬 王旭[1] 王文达[1] 郑国洋[1] 张玉石[1] Wang Zhan;Guo Hao;Cai Yi;Zhao Yang;Wang Xu;Wang Wenda;Zheng Guoyang;Zhang Yushi(Department of Urology,Peking Union Medical College Hospital,Chinese Academy of Medical Science,Peking Union Medical College,Beijing 100730,China;Department of Urology,Xiangya Hospital,Central South University,Changsha 410008,China)

机构地区：[1]中国医学科学院,北京协和医学院,北京协和医院泌尿外科,100730 [2]中南大学湘雅医院泌尿外科,长沙410008

出　　处：《中华泌尿外科杂志》2021年第12期925-931,共7页Chinese Journal of Urology

基　　金：国家自然科学基金(81670611、81800590)。

摘　　要：目的分析结节性硬化症相关肾血管平滑肌脂肪瘤(TSC-RAML)的环状RNA(circRNA)表达谱,构建竞争性内源性RNA(ceRNA)调控网络。方法根据2012年国际结节性硬化症共识小组确定的TSC诊断标准,收集2017年1月至2019年1月北京协和医院收治的TSC-AML患者的肿瘤组织及配对的正常肾组织各3例,分别利用circRNA、miRNA芯片技术和二代测序检测3对配对样本的circRNA、miRNA和mRNA并确定差异分子。分别对差异性circRNA分子的来源基因和mRNA分子做基因本体学(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。基于差异性circRNA、miRNA和mRNA,分别建立上调和下调的ceRNA调控网络。结果共筛选出330个上调和336个下调的差异性circRNA,8个上调和7个下调的miRNA,800个上调和1130个下调的mRNA。通过GO和KEGG富集分析,发现包括脂代谢、黏着斑和矿物质吸收等多条通路存在异常。最终确立以hsa_circ_0092022、hsa_circ_0076859、hsa_circ_0033388引导的上调和由hsa_circ_0000374、hsa_circ_0000141、hsa_circ_0072665、hsa_circ_0009503、hsa_circ_0000009引导的下调ceRNA网络。结论TSC-RAML与配对的正常肾组织之间存在多个差异性表达的circRNA分子。ceRNA调控网络可能参与TSC-RAML的发生和发展。Objective To comprehensively analyze the expression profile of circular RNA(circRNA)and construct competing endogenous RNA(ceRNA)regulatory networks in tuberous sclerosis complex related renal angiomyolipoma(TSC-RAML).Methods According to the diagnostic criteria of TSC determined by the international consensus group on tuberous sclerosis in 2012,tumor tissues and paired normal renal tissues of 3 patients with TSC-RAML who were diagnosed in our hospital from January 2017 to January 2019 were collected.The circRNA,miRNA and mRNA of 3 paired samples were detected by circRNA,miRNA chip technology and next generation sequencing respectively,and the differential molecules were determined.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed based on differential mRNA molecules and host genes of circRNA.Based on differential circRNA,miRNA and mRNA,up-regulated and down-regulated ceRNA regulatory networks were established.Results A total of 330 up-regulated and 336 down-regulated differential circRNA,8 up-regulated and 7 down-regulated miRNA,800 up-regulated and 1130 down-regulated mRNA were screened.Through GO and KEGG enrichment analysis,many pathways including lipid metabolism,focal adhesion and mineral absorption were abnormally altered.Finally,the up-regualted ceRNA network led by hsa_circ_0092022,hsa_circ_0076859 and hsa_circ_0033388 and down-regulated network led by hsa_circ_0000374,hsa_circ_0000141,hsa_circ_0072665,hsa_circ_0009503 and hsa_circ_0000009 were constructed.Conclusions There were many differentially expressed circRNA between TSC-RAML and paired normal renal tissues.ceRNA regulatory networks may be involved in the occurrence and development of TSC-RAML.

关 键 词：结节性硬化症 肾血管平滑肌脂肪瘤 环状RNA 竞争性内源性RNA调控网络 

分 类 号：R596.1[医药卫生—内科学] R737.11[医药卫生—临床医学]