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山东大学学报 (医学版) ›› 2022, Vol. 60 ›› Issue (10): 27-32.doi: 10.6040/j.issn.1671-7554.0.2022.0152

• 临床医学 • 上一篇    下一篇

长链非编码RNA NONHSAT247814.1在18例儿童心肌炎中的表达及体外细胞实验观察

冯鑫鑫1,韩波1,2,张丽1,马孟洁1,陈思宇2   

  1. 1.山东大学齐鲁医学院, 山东 济南 250012;2.山东第一医科大学附属省立医院儿科, 山东 济南 250021
  • 发布日期:2022-09-30
  • 通讯作者: 韩波. E-mail:hanbo35@163.com
  • 基金资助:
    国家自然科学基金(81873498);泰山学者特聘专家(nots201511099)

Long non-coding RNA NONHSAT247814.1 expression in 18 childhood with myocarditis and in vitro cellular experimental observation

FENG Xinxin1, HAN Bo1,2, ZHANG Li1, MA Mengjie1, CHEN Siyu2   

  1. 1. Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China
  • Published:2022-09-30

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摘要： 目的 探讨儿童心肌炎潜在的诊断标志物并明确其在人心肌细胞炎症中的生物学功能。 方法 筛选儿童心肌炎基因芯片结果中差异表达的长链非编码RNA(LncRNA),继而扩大样本量进行验证后,确立目标分子。收集心肌炎患儿18例(儿童心肌炎组)及健康查体儿童18例(正常对照组)的基本资料及临床信息,采用实时定量聚合酶链反应(qRT-PCR)法检测目标分子的表达水平,绘制受试者操作曲线(ROC)判断目标分子用于诊断儿童心肌炎的价值。利用脂多糖刺激人心肌细胞(AC16)构建心肌细胞炎症模型,将小干扰RNA转染至AC16中抑制目标分子的表达。采用酶联免疫吸附(ELISA)法检测细胞上清中炎症因子及心肌损伤标志物的蛋白浓度,采用CCK8法检测细胞的增殖活性。 结果 确定NONHSAT247814.1为本研究的目标分子。NONHSAT247814.1在儿童心肌炎组的相对表达量高于正常对照组(P<0.01),其在急性期的相对表达量高于恢复期。与外周循环中的N端脑钠肽前体呈正相关(R2=0.40, P=0.005),与左心室射血分数呈负相关(R2=-0.53, P=0.000 6); NONHSAT247814.1诊断儿童心肌炎的ROC曲线(AUC=0.89, P<0.001,灵敏度为83.33%,特异度为88.89%);在细胞水平,降低NONHSAT247814.1的表达,可以减少白介素-1β(IL-1β)、白介素-6(IL-6)、肌钙蛋白(cTnT)及B型利钠肽(BNP)的释放,增加细胞的增殖活性。 结论 NONHSAT247814.1具有儿童心肌炎诊断标志物潜力,抑制NONHSAT247814.1的表达,可以减轻LPS诱导的心肌细胞炎症损伤。

关键词: 长链非编码RNA, NONHSAT247814.1, 心肌炎, 诊断标志物, 儿童

Abstract: Objective To explore the potential diagnostic marker of child myocarditis and to clarify the biological functions in human cardiomyocyte inflammation. Methods Long non-coding RNAs(LncRNAs)differentially expressed in the results of pediatric myocarditis gene chips were screened, the sample size was expanded for validation, and the target molecule was identified. The basic data and clinical information of 18 children with myocarditis(myocarditis group)and 18 healthy children(normal control group)were collected, real-time quantitative polymerase chain reaction(qRT-PCR)was used to test the expression of the target molecule, and then the receiver operating characteristic(ROC)curve was plotted to evaluate the value of the target molecule in the diagnosis of pediatric myocarditis. Lipopolysaccharide was utilized to stimulate AC16 cells and then extoblish the model of inflammatory injury, and the small interfering RNA was transfected into AC16 to inhibit the expression of the target molecule. Enzyme-linked immunosorbent assay(ELIAS)was used to test the protein concentration of inflammatory factors and myocardial injury markers in the cell supernatants, and CCK8 was used to detect cellular proliferation. Results NONHSAT247814.1 was identified as the target molecule. The relative expression of NONHSAT247814.1 was higher in the myocarditis group than in normal control group(P<0.001). The relative expression was higher in acute phase than in recovery phase, and positively correlated with NT-pro brain natriuretic peptide in the peripheral circulation(R2=0.40, P=0.005), but negatively correlated with left ventricular ejection fraction(R2=-0.53, P=0.0006). ROC for NONHSAT247814.1 in diagnosing myocarditis was(AUC=0.89, P<0.001, sensitivity=83.33% and specificity=88.89%). At the cellular level, reducing the expression of NONHSAT247814.1 attenuated the release of interleukin-1β, interleukin-6, troponin T and brain natriuretic peptide, while increased the cellular proliferation. Conclusion NONHSAT247814.1 has potential as a diognostic marker for myocarditis in children, inhibiting of NONHSAT247814.1 expression attenuates LPS-induced inflommation iujury in cardiomyocytes effects at the cellular level.

Key words: Long non-coding RNA, NONHSAT247814.1, Myocarditis, Diagnostic marker, Children

中图分类号: 

  • R725.4
[1] Wang J, Han B. Dysregulated CD4+ T Cells and microRNAs in Myocarditis[J]. Front Immunol, 2020, 11: 539.doi:10.3389/fimmu.2020.00539.
[2] Law YM, Lal AK, Chen S, et al. Diagnosis and management of myocarditis in children: a scientific statement from the American Heart Association[J]. Circulation, 2021, 144(6): e123-e135.
[3] Ammirati E, Frigerio M, Adler ED, et al. Management of acute myocarditis and chronic inflammatory cardiomyopathy: an expert consensus document[J]. Circ Heart Fail, 2020, 13(11): e007405. doi:10.1161/CIRCHEARTFAILURE.120.007405.
[4] Tschope C, Ammirati E, Bozkurt B, et al. Myocarditis and inflammatory cardiomyopathy: current evidence and future directions[J]. Nat Rev Cardiol, 2021, 18(3): 169-193.
[5] Abrar S, Ansari MJ, Mittal M, et al. Predictors of mortality in paediatric myocarditis[J]. J Clin Diagn Res, 2016, 10(6): SC12-16.
[6] 庄士心, 黄国英. 儿童暴发性心肌炎早期诊断及治疗进展[J]. 中国小儿急救医学, 2019, 26(10): 777-781.
[7] Kociol RD, Cooper LT, Fang JC, et al. Recognition and initial management of fulminant myocarditis: a scientific statement from the American Heart Association[J]. Circulation, 2020, 141(6): e69-e92.
[8] 杜甜甜, 李娟, 赵颖慧, 等. 长链非编码RNA LINC02474在结直肠癌中的表达特征及对细胞增殖的影响[J]. 山东大学学报(医学版), 2021, 59(10): 57-67. DU Tiantian, LI Juan, ZHAO Yinghui, et al. Expression profiles of long non-coding RNA LINC02474 and effects on cell proliferation in colorectal cancer[J]. Journal of Shandong University(Health Sciences), 2021, 59(10): 57-67.
[9] 张学丽, 郑璐, 王瑜, 等. 沉默LncRNA H19通过调节神经生长因子抑制心肌梗死后交感神经重构[J]. 山东大学学报(医学版), 2021, 59(5): 73-81. ZHANG Xueli, ZHENG Lu, WANG Yu, et al. Knockdown of LncRNA H19 inhibits sympathetic nerve remodeling after myocardial infarction by regulating nerve growth factor[J]. Journal of Shandong University(Health Sciences), 2021, 59(5): 73-81.
[10] Wadley GD, Lamon S, Alexander SE, et al. Noncoding RNAs regulating cardiac muscle mass[J]. J Appl Physiol(1985), 2019, 127(2): 633-644.
[11] Gandhi S, Ruehle F, Stoll M. Evolutionary patterns of non-coding RNA in cardiovascular biology[J]. Noncoding RNA, 2019, 5(1): 15. doi: 10.3390/ncrna5010015.
[12] Li B, Hu Y, Li X, et al. Sirt1 antisense long noncoding RNA promotes cardiomyocyte proliferation by enhancing the stability of Sirt1[J]. J Am Heart Assoc, 2018, 7(21): e009700. doi: 10.1161/JAHA.118.009700.
[13] Yeh CF, Chang YE, Lu CY, et al. Expedition to the missing link: long noncoding RNAs in cardiovascular diseases[J]. J Biomed Sci, 2020, 27(1): 48. doi: 10.1186/s12929-020-00647-w.
[14] Boeckel JN, Perret MF, Glaser SF, et al. Identification and regulation of the long non-coding RNA Heat2 in heart failure[J]. J Mol Cell Cardiol, 2019, 126: 13-22. doi: 10.1016/j.yjmcc.2018.11.004.
[15] 中华医学会儿科学分会心血管学组,中华医学会儿科学分会心血管学组心肌炎协作组,中华儿科杂志编辑委员会,中国医师协会心血管医师分会儿童心血管专业委员会.儿童心肌炎诊断建议(2018年版)[J]. 中华儿科杂志, 2019, 57(2): 87-89.
[16] Liu Q, Kong Y, Han B, et al. Long Non-coding RNA expression profile and functional analysis in children with acute fulminant myocarditis[J]. Front Pediatr, 2019, 7: 283. doi: 10.3389/fped.2019.00283.
[17] Zhang L, Han B, Liu H, et al. Circular RNA circACSL1 aggravated myocardial inflammation and myocardial injury by sponging miR-8055 and regulating MAPK14 expression[J]. Cell Death Dis, 2021, 12(5): 487. doi: 10.1038/s41419-021-03777-7.
[18] 徐希奇, 田庄, 方全, 等. 北京协和医院经皮心内膜心肌活检临床操作规范[J]. 中华心血管病杂志, 2021, 49(1): 12-16.
[19] Chen Y, Sun Z, Xu L, et al. Diagnostic and prognostic value of cardiac magnetic resonance strain in suspected myocarditis with preserved LV-EF: a comparison between patients with negative and positive late gadolinium enhancement findings[J]. J Magn Reson Imaging, 2022, 55(4): 1109-1119.
[20] Butts RJ, Boyle GJ, Deshpande SR, et al. Characteristics of clinically diagnosed pediatric myocarditis in a contemporary multi-center cohort[J]. Pediatr Cardiol, 2017, 38(6): 1175-1182.
[21] Robinson EK, Covarrubias S, Carpenter S. The how and why of lncRNA function: an innate immune perspective[J]. Biochim Biophys Acta Gene Regul Mech, 2020, 1863(4): 194419.
[22] Guzmán-Rivera D, Liempi A, González-Herrera F, et al. Simvastatin improves cardiac function through Notch 1 activation in BALB/c mice with chronic chagas cardiomyopathy.[J]. Antimicrob Agents Chemother, 2020, 64(8): e02141-19.
[23] Yuan H, Du S, Deng Y, et al. Effects of microRNA-208a on inflammation and oxidative stress in ketamine-induced cardiotoxicity through Notch/NF-κB signal pathways by CHD9[J]. Biosci Rep, 2019, 39(5): BSR20182381.
[24] Zhao Y, Teng H, Yao F, et al. Challenges and strategies in ascribing functions to long noncoding RNAs[J]. Cancers(Basel), 2020, 12(6): 1458.
[25] Wang W, Min L, Qiu X, et al. Biological function of long non-coding RNA(lncRNA)Xist[J]. Front Cell Dev Biol, 2021, 9: 645647. doi: 10.3389/fcell.2021.645647.
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