大鼠肝再生中环状RNA的表达变化及其对细胞增殖的调节作用

doi:10.16098/j.issn.0529-1356.2021.02.009

解剖学报 ›› 2021, Vol. 52 ›› Issue (2): 216-224.doi: 10.16098/j.issn.0529-1356.2021.02.009

大鼠肝再生中环状RNA的表达变化及其对细胞增殖的调节作用

郭学强^1,2 郭建林^1,2 靳伟^1,2 常翠芳^1,2 徐存拴^1,2*陈广文^1*

1.河南师范大学生命科学学院； 2.细胞分化调控国家重点实验室培育基地，河南新乡 453007

收稿日期:2019-09-16 修回日期:2019-09-27 出版日期:2021-04-06 发布日期:2021-04-06
通讯作者: 徐存拴;陈广文 E-mail:gxqxll@163.com
基金资助:
4种共表达microRNA协同调节大鼠肝细胞增殖和肝再生的分子机制研究;秦岭山脉淡水三肠目涡虫分类和区系研究;海南岛淡水三肠目涡虫生态学及进化生物学研究;组织再生关键基因的筛选及功能研究—以日本三角涡虫为例

Expression profile of circularRNA during rat liver regeneration and its regulatory effect on cell proliferation

GUO Xue-qiang1, 2 GUO Jian-lin1, 2 JIN Wei1, 2 CHANG Cui-fang1, 2 XU Cun-shuan1, 2* CHEN Guang-wen1*#br#

1.College of Life Science, He’nan Normal University, He’ nan Xinxiang 453007, China; 2.State Key Laboratory Cultivation Base for Cell Differentiation Regulation, He’nan Normal University, He’nan Xinxiang 453007, China

Received:2019-09-16 Revised:2019-09-27 Online:2021-04-06 Published:2021-04-06
Contact: XU Cun-shuan;CHEN Guang-wen E-mail:gxqxll@163.com

摘要/Abstract

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TargetScan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，circRNA_03651、circRNA_03653、circRNA_04500、circRNA_05865、circRNA_11274、circRNA_13559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circRNA_03651、circRNA_03653、circRNA_04500、circRNA_05865、circRNA_11274、circRNA_13559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。

关键词: 肝再生, 细胞增殖, 竞争性内源RNA网络, 环状RNA, 生物高通量检测, 大鼠

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 TargetScan 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 regulate 6510 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 circRNA_03651, circRNA_03653, circRNA_04500, circRNA_05865, circRNA_11274 and circRNA_13559 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 circRNA_03651, circRNA_03653, circRNA_04500, circRNA_05865, circRNA_11274 and circRNA_13559 might play a crucial role on cell proliferation involved in rat LR via 12 miRNAs-15 mRNAs axis.

Key words: Liver regeneration, Cell proliferation, Competitive endogenous RNA network, Circular RNA, High-throughput sequencing, Rat

中图分类号:

Q954

郭学强郭建林靳伟常翠芳徐存拴陈广文 . 大鼠肝再生中环状RNA的表达变化及其对细胞增殖的调节作用[J]. 解剖学报, 2021, 52(2): 216-224.

GUO Xue-qiang GUO Jian-lin JIN Wei CHANG Cui-fang XU Cun-shuan CHEN Guang-wen. Expression profile of circularRNA during rat liver regeneration and its regulatory effect on cell proliferation[J]. Acta Anatomica Sinica, 2021, 52(2): 216-224.

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大鼠肝再生中环状RNA的表达变化及其对细胞增殖的调节作用

Expression profile of circularRNA during rat liver regeneration and its regulatory effect on cell proliferation

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