Sp1特异性调控先天性心脏病相关基因钙调磷酸酶调节蛋白1基因亚型的转录

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (2): 189-192.

Sp1特异性调控先天性心脏病相关基因钙调磷酸酶调节蛋白1基因亚型的转录

李晓勇, 宋来春, 陶超, 金晶, 许铭^*

武汉科技大学附属武汉亚洲心脏病医院心外科职业危害识别与控制湖北省重点实验室, 湖北武汉 430022

收稿日期:2020-01-06 修回日期:2020-04-30 出版日期:2021-02-05 发布日期:2021-01-19
通讯作者: ^*xu_ming83@126.com
基金资助:
湖北省卫生健康科研基金(WJ2019H238);武汉市卫生计生科研基金(WX18Q33,WX17B19);武汉中青年医学骨干人才培养工程

Sp1 specifically regulates the transcription of congenital heart disease associated gene RCAN1 isoform 1

LI Xiao-yong, SONG Lai-chun, TAO Chao, JIN Jing, XU Ming^*

Department of Cardiac Surgery, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan Asia Heart Hospital, Wuhan University of Science and Technology, Wuhan 430022, China

Received:2020-01-06 Revised:2020-04-30 Online:2021-02-05 Published:2021-01-19
Contact: ^*xu_ming83@126.com

摘要/Abstract

摘要： 目的探索先天性心脏病相关基因钙调磷酸酶调节蛋白1基因(RCAN1)两个亚型(RCAN1-1和 RCAN1-4)组织特异性表达的机制。方法通过生物信息学预测RCAN1-1和 RCAN1-4各自启动子区的转录因子结合位点,分析比对并筛选出具有差异的位点,通过定点突变及荧光素酶报告基因系统检测筛选出的位点活性。将鉴定的转录因子的抑制剂与RCAN1表达载体作用,分为实验组(抑制剂+)和对照组(抑制剂-),通过实时荧光定量PCR检测RCAN1亚型mRNA的表达量。结果在RCAN1-1启动子区-138GCCCGCCGCC-129处检测出一个新的、未报道过的具有活性的转录因子Sp1结合位点。实验组RCAN1-1 mRNA 表达量低于对照组(P＜0.001),而两组RCAN1-4 mRNA的表达量无差异。结论 Sp1特异性调控RCAN1-1的转录,增强其表达,而对RCAN1-4无影响,提示其可作为将来基因治疗或检测的一个潜在靶点。

关键词: 先天性心脏病, Sp1, RCAN1, 转录, 基因

Abstract: Objective To investigate the regulatory mechanism of regulator of calcineurin 1 (RCAN1), which is associated with congenital heart disease and has a tissue-specific expression pattern. Methods The transcription factor binding sites were predicted and compared in promoter of RCAN1. The site directed mutation and luciferase assay were used to detect the activity of the binding site. Then the transcriptional regulation of RCAN1 by Sp1 was evaluated by real-time quantitative PCR under physiological condition (control group) or Sp1 inhibitor (experimental group). Results The Sp1 binding site-138GCCCGCCGCC-129 was predicated and identified. The RCAN1-1 mRNA was more decreased in experimental group than the control group (P＜0.001). There was no significant difference in RCAN1-4 mRNA between the two groups. Conclusions Sp1 specifically regulates the transcription of RCAN1-1 isoform, which demonstrates that Sp1 is a potential targete molecule for genetic testing and clinical intervention for congenital heart disease.

Key words: congenital heart disease, Sp1, RCAN1, transcription, gene

中图分类号:

R654.2

李晓勇, 宋来春, 陶超, 金晶, 许铭. Sp1特异性调控先天性心脏病相关基因钙调磷酸酶调节蛋白1基因亚型的转录[J]. 基础医学与临床, 2021, 41(2): 189-192.

LI Xiao-yong, SONG Lai-chun, TAO Chao, JIN Jing, XU Ming. Sp1 specifically regulates the transcription of congenital heart disease associated gene RCAN1 isoform 1[J]. Basic & Clinical Medicine, 2021, 41(2): 189-192.

参考文献

[1] Lynch Á, Ng L, Lawlor P, et al. Cyanotic congenital heart disease modes of presentation and prenatal detection [J]. Ir Med J, 2019, 112:1019.
[2] Baraona F, Gurvitz M, Landzberg MJ, et al. Hospitalizations and mortality in the United States for adults with down syndrome and congenital heart disease [J]. Am J Cardiol, 2013, 111: 1046-1051.
[3] Wu Y, Song W. Regulation of RCAN1 translation and its role in oxidative stress-induced apoptosis [J]. FASEB J, 2013, 27: 208-221.
[4] Peiris H, Keating DJ. The neuronal and endocrine roles of RCAN1 in health and disease [J]. Clin Exp Pharmacol Physiol, 2018, 45: 377-383.
[5] Li X, Wang G, An Y, et al. Association between sequence variations in RCAN1 promoter and the risk of sporadic congenital heart disease in a Chinese population [J]. Pediatr Cardiol, 2015, 36: 1393-1399.
[6] Li X, Shi L, Xu M, et al. RCAN1 mutation and functional characterization in children with sporadic congenital heart disease [J]. Pediatr Cardiol, 2018, 39: 226-235.
[7] Nappi F, Singh SSA. Gene therapy and regenerative tissue engineering in congenital heart disease [J]. Transl Pediatr, 2019, 8:356-359.
[8] 王凤. 先天性心脏病相关致病基因调控区变化的研究进展 [J]. 国际儿科学杂志, 2017, 44: 77-79.
[9] Sarioğlu T, Erek E, Yalçinbaş YK. Why national databases are necessary for pediatric and congenital heart surgery practice? [J]. Turk Gogus Kalp Damar Cerrahisi Derg, 2019, 27:418-422.
[10] Cheng L, Li P, Wang H, et al. Decreased activity of RCAN1.4 is a potential risk factor for congenital heart disease in a Han Chinese population [J]. Protein Cell, 2018, 9:1039-1044.
[11] 欧阳娜, 田鹤锋, 刘玲娟, 等. HIF-1α基因启动子-1946位点基因多态性与紫绀型先天性心脏病低氧耐受的相关性分析 [J]. 基础医学与临床, 2017, 37:355-359.
[12] Villahoz S, Yunes-Leites PS, Méndez-Barbero N, et al. Conditional deletion of Rcan1 predisposes to hypertension-mediated intramural hematoma and subsequent aneurysm and aortic rupture [J]. Nat Commun, 2018, 9:4795.

[1]	郑凯, 任华亮, 张望德, 李春民. 单细胞RNA测序技术在主动脉扩张性疾病中的应用[J]. 基础医学与临床, 2022, 42(7): 1139-1143.
[2]	刘旭, 常德, 王俊锋. 功能基因筛选和鉴定策略的研究进展及其优缺点[J]. 基础医学与临床, 2022, 42(6): 969-974.
[3]	李晓光, 杨璐, 刘旭东, 贾鑫淼, 程燕飞, 崔丽英. 炎性细胞因子在肌萎缩侧索硬化诊断治疗中的研究进展[J]. 基础医学与临床, 2022, 42(6): 964-968.
[4]	武坤, 聂波, 李云涛, 杨金荣, 程沈菊, 李艳红, 史明霞. 外周血miR-200c水平对移植异基因造血干细胞后急性移植物抗宿主病发生的预测作用[J]. 基础医学与临床, 2022, 42(6): 871-875.
[5]	周岚, 张生贵, 胡祖梁, 王添贤, 岳鹏鹏, 于鸿浩. 基于CRISPR/Cas9系统高效编辑小鼠miR let-7a[J]. 基础医学与临床, 2022, 42(6): 857-863.
[6]	谢利华, 杨奇, 李雅倩, 谢心悦, 雷诗娟, 周琳. 转录因子Kaiso下调人乳腺癌细胞系中lncRNA MEG3的表达[J]. 基础医学与临床, 2022, 42(5): 758-762.
[7]	田晓怡, 刘颖, 姚瑶, 顾秀丽, 李爱华, 郑胡镛, 宋文琪. 儿童急性淋巴细胞白血病ABCB1、ABCC4和SLCO1B1多态性与大剂量MTX血药浓度及不良反应的相关性[J]. 基础医学与临床, 2022, 42(5): 708-713.
[8]	陈仲扬, 马艳妮, 余佳. 基于单细胞转录组测序分析描绘人类早期胚胎红细胞发育图谱[J]. 基础医学与临床, 2022, 42(5): 776-781.
[9]	赵川榕, 周菁. 靶向剪切力敏感关键分子的动脉粥样硬化防治研究[J]. 基础医学与临床, 2022, 42(3): 378-383.
[10]	吕雪, 李雪薇, 杨婷, 郑锦秀, 祝子鹤, 杨涛, 徐钧. 食管胃结合部腺癌生物信息学分析及Involucrin基因突变位点筛选[J]. 基础医学与临床, 2022, 42(2): 235-242.
[11]	冯天瑞, 严维刚. 环状RNAs在前列腺癌中的研究进展[J]. 基础医学与临床, 2022, 42(1): 179-183.
[12]	陈号, 陈韬, 吴静. IL-6/JAK/STAT3信号通路在前列腺癌发展和治疗中的研究进展[J]. 基础医学与临床, 2022, 42(1): 159-162.
[13]	霍明珠, 张轶乐, 徐家伟, 史昊, 刘益栋, 牛文彬. PATL2复合杂合变异致卵母细胞成熟障碍[J]. 基础医学与临床, 2022, 42(1): 51-55.
[14]	滕培英, 李静, 师玉露, 杨帆, 欧霞, 陈伟. 柯萨奇病毒B组5型感染的人恶性胚胎横纹肌肉瘤细胞系lncRNA表达谱分析[J]. 基础医学与临床, 2022, 42(1): 68-74.
[15]	刘健. 基因治疗中的核酸药物及非病毒递送载体的研究进展[J]. 基础医学与临床, 2022, 42(1): 41-50.