[1]赵恒 谭琦 杜晓宇 谷泽慧 王亚帝.蒽环类药物致心脏毒性潜在的生物标志物研究[J].心血管病学进展,2022,(3):282-288.[doi:10.16806/j.cnki.issn.1004-3934.2022.03.000]
 ZHAO HengTAN QiDU XiaoyuGU ZehuiWANG Yadi.Potential Biomarkers of Anthracycline-Induced Cardiotoxicity[J].Advances in Cardiovascular Diseases,2022,(3):282-288.[doi:10.16806/j.cnki.issn.1004-3934.2022.03.000]
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蒽环类药物致心脏毒性潜在的生物标志物研究()
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2022年3期
页码:
282-288
栏目:
论著
出版日期:
2022-03-25

文章信息/Info

Title:
Potential Biomarkers of Anthracycline-Induced Cardiotoxicity
文章编号:
202105019
作者:
赵恒1 谭琦2 杜晓宇1 谷泽慧2 王亚帝3
(1.锦州医科大学第三临床学院,辽宁 锦州 121000;2.锦州医科大学附属第三医院病理科,辽宁 锦州 121000;3.锦州医科大学附属第三医院精准医学科,辽宁 锦州121000)
Author(s):
ZHAO Heng1TAN Qi2DU Xiaoyu1GU Zehui2WANG Yadi3
(1.The Third Clinical College of Jinzhou Medical University,Jinzhou 121000,Liaoning,China; 2.Department of Pathology,The Third Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000,Liaoning,China; 3.Department of Precision Medicine,The Third Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000,Liaoning,China)
关键词:
生物信息学乳腺癌心脏毒性信使RNA
Keywords:
BioinformaticsBreast cancerCardiotoxicitymiRNA
DOI:
10.16806/j.cnki.issn.1004-3934.2022.03.000
摘要:
目的 对蒽环类药物致心脏毒性相关的基因表达数据集进行分析,寻找关键调控信使RNA(mRNA)及靶向微小RNA(miRNA),为蒽环类药物致心肌损伤提供早期诊断标志物。方法 利用GEO数据库获得蒽环类药物所致心脏毒性的相关基因表达谱数据(GSE76314),其对特异性人诱导多能干细胞源性心肌细胞使用0 μmol(A组)、1 μmol(B组)阿霉素诱导24 h的mRNA表达数据进行差异性分析,获得差异性mRNA表达谱;通过基因本体功能注释及京都基因和基因组百科全书(KEGG)信号通路富集分析差异表达mRNA发挥的功能;对所有差异表达基因进行二次筛选,界定|FC|>2为明显差异表达基因,分别对上调和下调基因进行靶向miRNA预测。筛选出目标miRNA,使用5 μmol 吡柔比星诱导人心肌细胞后,通过qPCR验证目标miRNA表达情况。结果 数据集GSE76314得到上调基因10个,下调基因7个(|FC|>2,P<0.05),基因本体分析发现,差异表达基因主要在细胞黏附及脂质代谢等方面发挥调控作用;KEGG通路富集差异表达基因主要参与PPAR、p53和甾体生物合成等信号通路。对明显差异表达基因经miRanda和TargetScan软件进行靶向miRNA预测,选取条件为Score>170,Energe<﹣30,发现miR-1273g-3p是金属硫蛋白1F与S期激酶相关蛋白2的共同靶向miRNA,miR-1273g-3p可能在蒽环类药物导致的心肌损伤中发挥重要的调控作用。qPCR结果显示,经吡柔比星诱导后的人心肌细胞中miR-1273g-3p表达水平明显高于对照组。结论 miR-1273g-3p可能通过重点调控金属硫蛋白1F和S期激酶相关蛋白2在蒽环类药物致心肌损伤的发生和发展中发挥重要作用,成为蒽环类药物致心肌损伤的有效的临床标志物。
Abstract:
Objective To analyze the gene expression data set related to cardiotoxicity caused by anthracyclines,find key regulatory mRNA and targeted miRNA,and provide early diagnostic markers for myocardial injury caused by anthracyclines. Methods The GEO database was used to obtain anthracycline-induced cardiotoxicity-related gene expression profile data(GSE76314), which used 0 μmol (group A), 1 μmol (group B) for specific human induced pluripotent stem cell-derived cardiomyocytes doxorubicin-induced mRNA expression data for 24 hours for differential analysis to obtain differential mRNA expression profiles. The function of differentially expressed mRNA was analyzed by gene ontology(GO) function annotation and signal pathway enrichment of Kyoto Encyclopedia of Genes and Genomes(KEGG). All differentially expressed genes were screened again,and |FC|>2 was defined as significantly differentially expressed genes. The up-regulated and down-regulated genes were predicted by targeted miRNA respectively. After screening out the target miRNA, using 5 μmol THP to induce human cardiomyocyte,the expression of the target miRNA was verified by qPCR. Results In the data set GSE76314,10 up-regulated genes and 7 down-regulated genes were obtained(|FC|>2, P<0.05). GO analysis found that differentially expressed genes mainly play a regulatory role in cell adhesion and lipid metabolism. The enrichment of differentially expressed genes in the KEGG pathway is mainly involved in signal pathways such as PPAR,p53 and steroid biosynthesis. Targeted miRNAs were predicted by miRanda and TargetScan software for obviously differentially expressed genes,and the conditions of Score>170 and Energe<﹣30 were selected,and it was found that miR-1273g-3p is the co-targeting miRNA of metallothionein 1F and S-phase kinase related protein 2,and miR-1273g-3p may play an important regulatory role in anthracycline-induced myocardial injury. The qPCR results showed that the expression level of miR-1273g-3p in human cardiomyctes induced by THP was significantly higher than that in the control group. Conclusion miR-1273g-3p may play an important role in the occurrence and development of anthracycline-induced myocardial injury through the key regulation of metallothionein 1F and S-phase kinase related protein 2,and become an effective clinical marker of anthracycline-induced myocardial injury

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备注/Memo

备注/Memo:
收稿日期:2021-05-08基金项目:辽宁省大学生创新基金(201710160000012)

通信作者:王亚帝,E-mailyadi2006215@126.com

更新日期/Last Update: 2022-04-20