miRNAs可能通过调控MAPK通路参与心室间隔缺损

doi:10.16352/j.issn.1001-6325.2022.04.006

基础医学与临床 ›› 2022, Vol. 42 ›› Issue (4): 590-598.doi: 10.16352/j.issn.1001-6325.2022.04.006

miRNAs可能通过调控MAPK通路参与心室间隔缺损

江辉, 张林^*

浙江中医药大学生命科学学院,浙江杭州 310053

收稿日期:2021-04-25 修回日期:2021-08-13 出版日期:2022-04-05 发布日期:2022-04-01
通讯作者: * 19493831@qq.com
基金资助:
浙江省教育厅高校国内访学者教师专业发展项目(FX2019021);浙江中医药大学科研创新人才项目(KC201921)

miRNAs may involve in ventricular septal defect through regulating the MAPK pathway

JIANG Hui, ZHANG Lin^*

College of Life Sciences, Zhejiang Chinese Medicial University, Hangzhou 310053, China

Received:2021-04-25 Revised:2021-08-13 Online:2022-04-05 Published:2022-04-01
Contact: * 19493831@qq.com

摘要/Abstract

摘要： 目的探讨miRNAs在心室间隔缺损(VSD)中发挥的作用。方法通过miRNAs表达谱芯片实验分析心室间隔缺损(VSD)组和健康组全血样本中的差异表达miRNAs,通过生物信息数据库miRbase、Targetscan和 Miranda进行靶基因测预。通过KEGG和REACTOME通路数据库筛选靶基因信号通路;采用RT-qPCR和Western blot检测关键信号通路中关键基因转录和蛋白表达水平。结果实验共得到22例差异表达miRNAs,预测获得12 744个靶基因;共得到126条通路,对其中与心脏发育密切相关的MAPK通路进行了深入分析,其中ERK子通路中的RASA1、NF1的转录和蛋白表达水平均明显增加(P＜0.05);Ras的转录和蛋白表达水平均明显降低(P＜0.05);ERK、MEK1磷酸化蛋白表达水平显著下降(P＜0.05);p38/MAPK子通路中的TNF、TNFRSF1A、TRAF2的转录和蛋白表达水平均明显增加(P＜0.05);p38磷酸化蛋白表达水平显著上升(P＜0.05);MEF2C的转录、总蛋白及磷酸化蛋白表达水平均明显上升(P＜0.05)。上述通路受到12个miRNAs调控。结论 22个差异miRNAs表达异常,导致多种已知心脏发育相关基因表达紊乱;其中12个表达异常miRNAs抑制ERK通路进而抑制心肌细胞分化、过度激活p38/MAPK通路表达进而促进心肌细胞异常凋亡,最终导致VSD的发生。

关键词: 心室间隔缺损, 差异表达miRNAs, MAPK通路

Abstract: Objective To investigate the role of miRNAs in pathogenesis of ventricular septal defect. Methods The miRNAs differential expression in whole blood samples from ventricular septal defect (VSD) group and normal group was analyzed by miRNAs expression microarray experiment and the target genes were predicted by biological information databases miRbase, Targetscan and Miranda. Target gene signaling pathways were screened through KEGG and REACTOME pathway databases, the transcription and protein expression of key genes in key signaling pathways were detected by RT-qPCR and Western blot. Results A total of 22 cases of differentially expressed miRNA were obtained in the experiment, and 12 744 target genes were predicted. A total of 126 pathways were found and the MAPK pathway, which was closely related to heart development, and was deeply analyzed. Among them, the transcription and protein expression of RASA1 and NF1 in ERK pathway were significantly increased (P＜0.05), the transcription and protein expression of RAS were significantly decreased(P＜0.05), and the expression levels of ERK and MEK1 phosphorylated proteins were also significantly decreased(P＜0.05); the transcription and protein expression of TNF, TNFRSF1A and TRAF2 in the p38/MAPK sub-pathway were significantly increased(P＜0.05), the expression of p38 phosphorylated proteins was significantly increased(P＜0.05), The transcrip-tion, total protein and phosphorylated protein expression of MEF2C were significantly increased(P＜0.05). The above pathways were found to be regulated by 12 miRNA. Conclusions The abnormal expression of 22 differentially expressed miRNAs leads to a variety of known cardiac development-related gene expression disorders. Among them, 12 abnormally expressed miRNAs inhibit the ERK pathway and thus inhibit the differentiation of cardiomyocytes and over-activate the expression of p38/MAPK pathway to promote the abnormal apoptosis of cardiomyocytes, and ultimately lead to the occurrence of VSD.

Key words: ventricular septal defect, differentially expressed miRNAs, MAPK pathway

中图分类号:

江辉, 张林. miRNAs可能通过调控MAPK通路参与心室间隔缺损[J]. 基础医学与临床, 2022, 42(4): 590-598.

JIANG Hui, ZHANG Lin. miRNAs may involve in ventricular septal defect through regulating the MAPK pathway[J]. Basic & Clinical Medicine, 2022, 42(4): 590-598.

参考文献

[1] 李振,喻卓.先天性心脏病病因学的研究进展[J].临床医学,2018,38:118-122+126.
[2] 张炼. 先天性心脏病遗传学基础研究进展[J]. 中华实用儿科临床杂志, 2016, 31:969-972.
[3] 惠增骞,仇小强.室间隔缺损病因和致病机理的研究现状及展望[J].实用预防医学,2010,17:2332-2334.
[4] 滕新栋,陈晓光,姜华,等.miRNAs在活动性肺结核患者和健康人血浆中的差异表达[J].基础医学与临床,2018,38:1590-1592.
[5] 段乐, 候宗柳, 李秦瑞,等. miRNA在先天性心脏病中的研究进展[J]. 医学信息, 2015,11:358.
[6] Burotto M, Chiou VL, Lee J, et al. The MAPK pathway across different malignancies: a new perspective[J]. Cancer, 2015, 120,3446-3456.
[7] 付程凯,李建民,赵宏涛,等.依达拉奉对蛛网膜下腔出血大鼠海马区神经细胞p-ERK1/2蛋白及自噬的影响[J].新疆医科大学学报,2018,41:66-70.
[8] 李维玲,吴敬波.心房利钠肽原不同肽段的抗肿瘤机制[J].肿瘤预防与治疗,2015,28:37-40.
[9] Mirza AM, Gysin S, Malek N, et al. Cooperative regulation of the cell division cycle by the protein kinases RAF and AKT[J]. Mol Cell Biol, 2004, 24:10868-10881.
[10] 乔谷媛,陈必良.1型神经纤维瘤基因抑癌机制的研究进展[J].医学综述,2016,22:4847-4851.
[11] 张嘉.TRAF2在TNF诱导细胞凋亡过程中的作用及其信号转导途径[J].中国肿瘤生物治疗杂志,2001,8:301-303.
[12] Barajas-Espinosa A, Basye A, Angelos MG, et al. Modula-tion of p38 kinase by DUSP4 is important in regulating cardiovascular function under oxidative stress[J]. Free Radic Biol Med,2015,89:170-181.
[13] Sethi G, Sodhi A. Role of p38 mitogen-activated protein kinase and caspases in UV-B-induced apoptosis of murine peritoneal macrophages[J]. Photochem Photobiol,2004,79:48-54.

miRNAs可能通过调控MAPK通路参与心室间隔缺损

miRNAs may involve in ventricular septal defect through regulating the MAPK pathway

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 4

编辑推荐

Metrics

本文评价

[1]	陈思, 杨富国, 彭红军, 曹卫乐, 王振宇. 丙泊酚减轻缺氧/复氧诱导的心肌细胞损伤[J]. 基础医学与临床, 2022, 42(4): 583-589.
[2]	吴梦娄鉴芳黄珮珺黄蕾孙瑞红潘世扬王芳. 卵巢癌细胞通过p38 MAPK通路促进CD8+调节T细胞的生成[J]. 基础医学与临床, 2016, 36(2): 167-172.
[3]	康清杰向征彭旭东王强汤为学. 钙释放激活钙通道调节分子1促进结肠癌细胞系SW480的增殖[J]. 基础医学与临床, 2014, 34(12): 1658-1664.
[4]	王宝玉孙曼怡林静娜. 胰岛素对大鼠结肠平滑肌细胞凋亡及MAPK通路的影响[J]. 基础医学与临床, 2013, 33(6): 726-730.