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 郭建林 靳伟 常翠芳 徐存拴 陈广文

解剖学报 ›› 2021, Vol. 52 ›› Issue (2) : 216-224.

PDF(5145 KB)
欢迎访问《解剖学报》官方网站!今天是 English
PDF(5145 KB)
解剖学报 ›› 2021, Vol. 52 ›› Issue (2) : 216-224. DOI: 10.16098/j.issn.0529-1356.2021.02.009
细胞和分子生物学

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* 
作者信息 +

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#
Author information +
文章历史 +

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。

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.

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

Key words

Liver regeneration / Cell proliferation / Competitive endogenous RNA network / Circular RNA / High-throughput sequencing / Rat

引用本文

导出引用
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 https://doi.org/10.16098/j.issn.0529-1356.2021.02.009
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 https://doi.org/10.16098/j.issn.0529-1356.2021.02.009
中图分类号: Q954    

参考文献

[1] Zimmermann A. Regulation of liver regeneration[J]. Nephrol Dial Transplant,2004, 19 (Suppl 4): iv6-10.
[2] Michalopoulos GK, DeFrances M. Liver regeneration[J]. Adv Biochem Eng Biotechnol,2005, 93: 101-134.
[3] Adamek B, ZalewskaZiob M, Strzelczyk JK, et al. Hepatocyte growth factor and epidermal growth factor activity during later stages of rat liver regeneration upon interferon alpha-2b influence[J]. Clin Exp Hepatol,2017, 3(1): 9-15.
[4] Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency[J]. Nature,2013, 495(7441): 333-338.
[5] Fanale D, Taverna S, Russo A, et al. Circular RNA in exosomes[J]. Adv Exp Med Biol,2018, 1087: 109-117.
[6] Xu Z, Li P, Fan L, et al. The potential role of circRNA in tumor immunity regulation and immunotherapy[J]. Front Immunol,2018, 9: 9.
[7] Li L, Guo J, Chen Y, et al. Comprehensive CircRNA expression profile and selection of key CircRNAs during priming phase of rat liver regeneration[J]. BMC Genomics,2017, 18(1): 80.
[8] Guo X, Jin W, Chang C, et al. Large-scale quantitative genomics analyzes the circRNA expression profile and identifies the key circRNA in regulating cell proliferation during the proliferation phase of rat LR[J]. Artif Cells Nanomed Biotechnol,2019, 47(1): 2957-2966.
[9] Higgins GM, Anderson AR. Experimental pathology of the liver: restoration of the liver of the white rat following partial surgical removal[J]. Arch Pathol,1931, 12: 17.
[10] Anders S, Reyes A, Huber W. Detecting differential usage of exons from RNA-seq data[J]. Genome Res,2012, 22(10): 2008-2017.
[11] Hansen TB, Jensen TI, Clausen BH, et al. Natural RNA circles function as efficient microRNA sponges[J]. Nature,2013, 495(7441): 384-388.
[12] John B, Enright AJ, Aravin A, et al. Human microRNA targets[J]. PLoS Biol,2004, 2(11): e363.
[13] Shi Y, Yang F, Wei S, et al. Identification of key genes affecting results of hyperthermia in osteosarcoma based on integrative ChIP-Seq/TargetScan analysis[J]. Med Sci Monit,2017, 23: 2042-2048.
[14] Inoue K. MicroRNA function in animal development[J]. Tanpakushitsu Kakusan Koso,2007, 52(3): 197-204.
[15] Huang DW, Sherman BT, Tan Q, et al. DAVID Bioinformatics resources: expanded annotation database and novel algorithms to better extract biology from large gene lists[J]. Nucleic Acids Res,2007, 35(Web Server issue): W169-175.
[16] Michalopoulos GK. Advances in liver regeneration[J]. Expert Rev Gastroenterol Hepatol,2014, 8(8): 897-907.
[17] Zhang XO, Wang HB, Zhang Y, et al. Complementary sequence-mediated exon circularization[J]. Cell,2014, 159(1): 134-147.
[18] Zang XY, Geng XF, Zhang ChY, et al. Role of MicroRNAs in liver regeneration[J]. Acta Anatomica Sinica, 2017, 48(2): 230-235. (in Chinese)
臧夏炎, 耿小芳, 张春艳, 等. microRNAs在肝再生中的作用研究进展[J]. 解剖学报,2017, 48(2): 230-235.
[19] Choudhury R, Bonacci T, Wang X, et al. The E3 ubiquitin ligase SCF(Cyclin F) transmits AKT signaling to the cell-cycle machinery[J]. Cell Rep,2017, 20(13): 3212-3222.
[20] Du Q, Hu B, Feng Y, et al. CircOMA1-mediated mir-145-5p suppresses tumor growth of nonfunctioning pituitary adenomas by targeting TPT1[J]. J Clin Endocrinol Metab,2019, 104(6): 2419-2434.
[21] Sun M, Zhao W, Chen Z, et al. Circ_0058063 regulates CDK6 to promote bladder cancer progression by sponging miR-145-5p[J]. J Cell Physiol, 2019, 234(4): 4812-4824.
[22] Browne AJ, Gobel A, Thiele S, et al. p38 MAPK regulates the Wnt inhibitor Dickkopf-1 in osteotropic prostate cancer cells[J]. Cell Death Dis,2016, 7: e2119.
[23] Sun GL, Li Z, Wang WZ, et al. MiR-324-3p promotes gastric cancer development by activating Smad4-mediated Wnt/beta-catenin signaling pathway[J]. J Gastroenterol,2018, 53(6): 725-739.
[24] Jiao Y, Ye DZ, Li Z, et al. Protein tyrosine phosphatase of liver regeneration-1 is required for normal timing of cell cycle progression during liver regeneration[J]. Am J Physiol Gastrointest Liver Physiol,2015, 308(2): G85-91.
[25] Wang Y, Yang Z, Wang L, et al. MiR-532-3p promotes hepatocellular carcinoma progression by targeting PTPRT[J]. Biomed Pharmacother,2019, 109: 991-999.
[26] Liu H, Chen F, Zhang L, et al. A novel all-trans retinoic acid derivative 4-amino2trifluoromethyl-phenyl retinate inhibits the proliferation of human hepatocellular carcinoma HepG2 cells by inducing G0/G1 cell cycle arrest and apoptosis via upregulation of p53 and ASPP1 and downregulation of iASPP[J]. Oncol Rep,2016, 36(1): 333-341.

基金

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

PDF(5145 KB)

Accesses

Citation

Detail

段落导航
相关文章

/