【摘要】 目的探讨环状RNA（circRNA）在大鼠肝再生中的表达变化及其对细胞增殖的调节作用。方法用生物高通量检测方法分析114只2/3肝切除大鼠诱导的大鼠肝再生中circRNA的表达变化,用miRanda和Target Scan网站分析大鼠肝再生的靶微小RNA（miRNA）及其mRNA,用基因本体论（GO）和IPA软件分析大鼠肝再生涉及的生理活动和信号通路,用Cytoscape v3.0.2软件构建大鼠肝再生的相互作用网络,用表达模式结合靶miRNA数量和功能挑选候选关键circRNA。结果在大鼠再生肝材料中检测到20 878个circRNA,其中,560个发生差异表达,它们中的126个能与117个靶miRNA结合,后者调节6510个下游靶mRNA。这些靶mRNA涉及细胞增殖、应激反应、物质代谢等生理活动和转化生长因子β（TGF-β）、蛋白激酶A（PKA）、Wnt/β-连环蛋白（β-catenin）等信号通路。其中,circRNA₀3651、circRNA₀3653、circRNA₀4500、circRNA₀5865、circRNA₁1274、circRNA₁3559等6种circRNA可能通过12种miRNA调节15种mRNA进而在大鼠肝再生涉及的细胞增殖中发挥作用,视为大鼠肝再生的候选关键circRNA。结论大鼠肝再生中560个circRNA发生差异表达,其中circRNA₀3651、circRNA₀3653、circRNA₀4500、circRNA₀5865、circRNA₁1274、circRNA₁3559等6种circRNA通过12种miRNA和15种mRNA的相互作用网络支配大鼠肝再生涉及的细胞增殖。更多还原

【Abstract】 Objective This study aims to investigate the expression profile and regulatory effect on cell proliferation of circular RNA （circRNA） in rat liver regeneration （LR）. Methods CircRNA expression profile during rat LR of 114 rats’ regenerating liver which induced by 2/3 partial hepatectomy was detected by high-throughput sequencing.MiRanda and Target Scan were performed to predict their target microRNA （miRNAs） and mRNAs. Gene Ontology （GO）and IPA were used to analyze the physiological activities and signaling pathways they involved. Cytoscape v3. 0. 2 was used to construct the interaction network. Finally,the candidate key circRNAs were selected by the expression pattern combining with the number and function of target miRNAs. Results 20 878 circRNAs were detected during rat LR,among which 560 of them were differentially expressed,and 126 of them could bind to 117 target miRNAs,which were in turn to regulate6510 downstream target mRNAs. They were involved in cell proliferation,stress response,substance metabolism and transforming growth factor-β （TGF-β）,protein kinase A （PKA）,Wnt/beta-catenin signaling pathways. 6 differential expressed circRNAs,including circRNA₀3651,circRNA₀3653,circRNA₀4500,circRNA ₀5865,circRNA ₁1274 and circRNA₁3559 might play a pivotal role in cell proliferation involved in rat LR by regulating 12 miRNAs and 15 mRNAs. Resultsing they were regarded as the candidate key circRNAs of rat LR. Conclusion 560 circRNAs were differentially expressed in rat LR,among which circRNA₀3651,circRNA₀3653,circRNA₀4500,circRNA ₀5865,circRNA₁1274 and circRNA₁3559 might play a crucial role on cell proliferation involved in rat LR via 12 miRNAs-15 mRNAs axis.更多还原