大鼠肝再生启动阶段肝细胞CCAAT增强子结合蛋白β mRNA、微小RNA-369-3p和rno-Rmdn2_0006的表达和作用

doi:10.16098/j.issn.0529-1356.2021.06.011

解剖学报 ›› 2021, Vol. 52 ›› Issue (6): 913-916.doi: 10.16098/j.issn.0529-1356.2021.06.011

• 肝再生与细胞周期调控 • 上一篇下一篇

大鼠肝再生启动阶段肝细胞CCAAT增强子结合蛋白β mRNA、微小RNA-369-3p和rno-Rmdn2_0006的表达和作用

白格^1,2 王子慧^1,2 宋亚萍^1,2臧夏炎^1,2李亚霏^1,2 叶丙雨^1,2赵志虎^3* 徐存拴^1,2*

1.河南师范大学生命科学学院，河南新乡 453007; 2.河南省-科技部共建细胞分化调控国家重点实验室培育基地，河南新乡 453007; 3.军事医学研究院生物工程研究所，北京 100071

收稿日期:2021-01-04 修回日期:2021-03-12 出版日期:2021-12-06 发布日期:2021-12-06
通讯作者: 赵志虎;徐存拴 E-mail:cellkeylab@126.com

Expression and role of CCAAT enhancer binding protein β mRNA, microRNA-369-3p and rno-Rmdn2_0006 of hepatocytes during the rat liver regeneration initiation

BAI Ge^{1, 2} WANG Zi-hui^{1, 2} SONG Ya-ping^{1, 2} ZANG Xia-yan^{1, 2} LI Ya-fei^{1, 2}YE Bing-yu^{1, 2} ZHAO Zhi-hu^3*XU Cun-shuan ^{1, 2*}

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 Xinxiang 453007, China; 3. Institute of Biotechnology，Academy of Military Medical Sciences, Beijing 100071，China

Received:2021-01-04 Revised:2021-03-12 Online:2021-12-06 Published:2021-12-06
Contact: ZHAO Zhi-hu;XU Cun-shuan E-mail:cellkeylab@126.com

摘要/Abstract

摘要：

目的了解大鼠肝再生启动阶段CCAAT增强子结合蛋白β（CEBPβ）mRNA、miR-369-3p和rno-Rmdn2_0006调节肝细胞处于G0期还是G1期的途径和方法。方法按Higgins等方法制备大鼠2/3肝切除（PH）模型，按Smedsrod等方法分离肝细胞，用大规模定量分析技术检测大鼠肝再生中肝细胞竞争性内源RNA（ceRNA）表达的变化，用Cytoscape 3.2软件构建ceRNA的相互作用网络，用ceRNA综合分析等方法解析它们表达的相关性和作用相关性。结果 PH后0 h和 6 h时，CEBPβ mRNA的比值为1.11±0.11和2.57±0.10，miR-136-3p为0.70±0.22和0.28±0.03，rno-Rmdn2_0006为1.26±0.34和2.62±0.70。CEBPβ促进的G0期相关基因生长停滞和DNA损伤诱导型β（GADD45β）为0.12±0.09和2.50±0.44，细胞周期蛋白依赖性激酶抑制剂1A（CDKN1A）为0.39±0.07和0.93±0.15，抑制的G0期相关基因细胞周期蛋白依赖性激酶2相关蛋白2（CDK2AP2）为2.55±0.42和0.74±0.11，信号转导子和转录激活因子1（STAT1）为2.57±0.13和1.32±0.13。CEBPβ促进的G1期相关基因ETS变异转录因子6（ETV6）为0.77±0.05和2.22±0.68，血红蛋白加氧酶1（HMOX1）为1.05±0.21和4.57±0.88，丝裂原活化蛋白激酶14（MAPK14）为1.01±0.15和2.01±0.32，硫氧还蛋白相互作用蛋白（TXNIP）为1.03±0.07和2.50±0.19，抑制的G1期相关基因红细胞衍生核因子2样蛋白2（NFE2L2）为0.66±0.09和0.35±0.05。结论 PH后0 h时，CEBPβ mRNA未上调，有利于CEBPβ抑制的G0期相关基因表达和肝细胞处于G0期。相反，PH后6 h 时，rno-Rmdn2_0006和miR-369-3p通过相互作用解除了后者对CEBPβ mRNA的抑制，有利于CEBPβ形成，有利于CEBPβ促进的G1期相关基因表达和肝细胞处于G1期。

关键词: 肝再生, G0期肝细胞, G1期肝细胞, CCAAT增强子结合蛋白β, 竞争性内源RNA综合分析, 生物高通量检测, 大鼠

Abstract:

Objective To explore the pathways and patterns which CCAAT/enhancer binding protein β(CEBPβ) mRNA, miR-369-3p and rno-Rmdn2_0006 regulate the hepatocytes in G0 phase and G1 phase during rat liver regeneration (LR). Methods The rat 2/3 partial hepatectomy (PH) model was prepared as described by Higgins, the hepatocytes of rat liver right lobes were isolated in 9∶00-11∶00 am according to the method of Smedsrod et al, the large-scale quantitative detection of competitive endogenous RNA(ceRNAs) was processed by the high-throughput biotechnology, the interaction network of ceRNAs was constructed by Cytoscape 3.2 software, and the correlation in expression and role of ceRNAs was analyzed by ceRNA comprehensive analysis. Results It was found that at 0 hour and 6 hour after PH, the ratio value of CEBPβ mRNA showed 1.11±0.11 and 2.57±0.10, miR-136-3p displayed 0.70±0.22 and 0.28±0.03, rno-Rmdn2_0006 indicated 1.26±0.34 and 2.62±0.70. The G0 phase-related genes promoted by CEBPβ were following, the growth arrest and DNA damage inducible beta (GADD45β) 0.12±0.09 and 2.50±0.44, the cyclin dependent kinase inhibitor 1A(CDKN1A）0.39±0.07 and 0.93±0.15, but the G0 phase-related genes inbibited by CEBPβ were following, the cyclin dependent kinase 2 associated protein 2 (CDK2AP2) 2.55±0.42 and 0.74±0.11, the signal transducer and activator of transcription 1 (STAT1) 2.57±0.13 and 1.32±0.13. The G1 phase-related genes promoted by CEBPβ were following, the ETS variant transcription factor 6 (ETV6) 0.77±0.05 and 2.22±0.68, the hemoglobin oxygenase 1 (HMOX1) 1.05±0.21 and 4.57±0.88, the mitogen-activated protein kinase 14 (MAPK14) 1.01±0.15 and 2.01±0.32, the thioredoxin interacting protein (TXNIP) 1.03±0.07 and 2.50±0.19, but the G1 phase-related gene nuclear factor erythroid 2 like 2 (NFE2L2) inbibited by CEBPβ 0.66±0.09 and 0.35±0.05. Conclusion CEBPβ mRNA is not up-regulated at 0 hour after PH, that is helpful for the expression of the G0 phase-related genes inbibited by CEBPβ and for the hepatocytes to be in G0 phase. On the contrary, the interaction of miR-369-3p and rno-Rmdn2_0006 leads to CEBPβ mRNA to bind with miR-369-3p, to CEBPβ being formed probablely, and to the expression of the G1 phase-related genes promoted by CEBPβ probablely, and to the hepatocytes being in G1 phase at 6 hours after PH.

Key words: Liver regeneration, Hepatocyte in G0 phase, , Hepatocyte in G1 phase, CCAAT/enhancer binding protein β, Competitive endogenous RNA comprehensive analysis, Biological hig-throughput detection, Rat

中图分类号:

Q257

白格王子慧宋亚萍臧夏炎李亚霏叶丙雨赵志虎徐存拴 . 大鼠肝再生启动阶段肝细胞CCAAT增强子结合蛋白β mRNA、微小RNA-369-3p和rno-Rmdn2_0006的表达和作用[J]. 解剖学报, 2021, 52(6): 913-916.

BAI Ge WANG Zi-hui SONG Ya-ping ZANG Xia-yan LI Ya-fei YE Bing-yu ZHAO Zhi-hu XU Cun-shuan . Expression and role of CCAAT enhancer binding protein β mRNA, microRNA-369-3p and rno-Rmdn2_0006 of hepatocytes during the rat liver regeneration initiation[J]. Acta Anatomica Sinica, 2021, 52(6): 913-916.

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大鼠肝再生启动阶段肝细胞CCAAT增强子结合蛋白β mRNA、微小RNA-369-3p和rno-Rmdn2_0006的表达和作用

Expression and role of CCAAT enhancer binding protein β mRNA, microRNA-369-3p and rno-Rmdn2_0006 of hepatocytes during the rat liver regeneration initiation

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