基于整合miRNA-TF的调控网络分析揭示心力衰竭的关键基因-动脉网

Natrue：Regulatory network analysis based on integrated miRNA-TF reveals key genes in heart failure

Nature 等信源发布 2024-06-17 15:27

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AbstractThe etiology and pathophysiology of heart failure are still unknown. Increasing evidence suggests that abnormal microRNAs (miRNAs) and transcription factors (TFs) expression may be associated with the development of heart failure. Therefore, this study aims to explore key miRNAs, TFs, and related genes in heart failure to gain a greater understanding of the pathogenesis of heart failure.

摘要心力衰竭的病因和病理生理学尚不清楚。越来越多的证据表明，异常的microRNA（miRNA）和转录因子（TFs）表达可能与心力衰竭的发展有关。因此，本研究旨在探索心力衰竭中的关键miRNA，TF和相关基因，以更好地了解心力衰竭的发病机制。

To search and download the dataset of mRNA chips related to heart failure from the GEO database (GSE59867, GSE9128, and GSE134766), we analyzed differential genes and screened the common differentially expressed genes on two chips using R language software. The binary interactions and circuits among miRNAs, TFs, and corresponding genes were determined by Pearson correlation coefficient.

。通过Pearson相关系数确定miRNA，TF和相应基因之间的二元相互作用和电路。

A regulatory network of miRNAs, TFs, and target genes was constructed based on bioinformatics. By comparing the sequences of patients with and without heart failure, five downregulated genes with hypermethylated mRNA and three upregulated genes with hypomethylated mRNA were identified. The miRNA-TF gene regulatory network consisted of 26 miRNAs, 22 TFs and six genes.

基于生物信息学构建了miRNA，TF和靶基因的调控网络。通过比较患有和不患有心力衰竭的患者的序列，鉴定出五个具有高甲基化mRNA的下调基因和三个具有低甲基化mRNA的上调基因。miRNA-TF基因调控网络由26个miRNA，22个TF和6个基因组成。

GO and KEGG analysis results revealed that BP terms like cellular response to organic substance, cellular response to cytokine stimulus, and KEGG pathways like osteoclast differentiation, MAPK signaling pathway, and legionellosis were enriched of the DEGs. TMEM87A, PPP2R2A, DUSP1, and miR-92a have great potential as biomarkers for heart failure.

GO和KEGG分析结果显示，细胞对有机物质的反应，细胞对细胞因子刺激的反应以及破骨细胞分化，MAPK信号通路和军团菌病等KEGG途径等BP术语富含DEGs。TMEM87A，PPP2R2A，DUSP1和miR-92a作为心力衰竭的生物标志物具有很大的潜力。

The integrated analysis of the mRNA expression spectrum and microRNA-transcription factor-gene revealed the regulatory network of heart failure, which may provide clues to its alternative treatment..

mRNA表达谱和microRNA转录因子基因的综合分析揭示了心力衰竭的调控网络，这可能为其替代治疗提供线索。。

IntroductionHeart failure (HF) is a group of clinical syndromes caused by various cardiac structural or functional diseases, leading to absolute or relative decreases in cardiac output1. Epidemiologic data suggest that the incidence of heart failure in developed countries is approximately 1–2% of the adult population.

引言心力衰竭（HF）是由各种心脏结构或功能疾病引起的一组临床综合征，导致心输出量绝对或相对减少1。流行病学数据表明，发达国家心力衰竭的发病率约占成年人口的1-2%。

There are currently 22.5 million cases of heart failure worldwide, and the number of heart failure cases is increasing by two million every year2. Despite tremendous developments in medical technology, heart failure, as the final stage of most cardiovascular diseases, is the only cardiovascular disease whose incidence, morbidity, and mortality rates are increasing every year.Studies on silenced small RNAs have mainly followed two directions: small interfering RNAs (siRNAs) and microRNAs (miRNAs).

目前全世界有2250万例心力衰竭病例，心力衰竭病例每年增加200万例2。尽管医疗技术取得了巨大发展，但心力衰竭作为大多数心血管疾病的最后阶段，是唯一发病率，发病率和死亡率每年都在增加的心血管疾病。沉默小RNA的研究主要遵循两个方向：小干扰RNA（siRNA）和microRNA（miRNA）。

siRNAs are mainly involved in RNA interference with target mRNA, while miRNAs are more involved in regulating gene expression and play greater roles in this capacity. siRNA, which is processed by the specific endonuclease dicer, allows for the selective reduction of specific protein production via RNA interference silencing complex3.

siRNA主要参与靶mRNA的RNA干扰，而miRNA更多地参与调节基因表达，并在这种能力中发挥更大的作用。由特异性核酸内切酶dicer处理的siRNA允许通过RNA干扰沉默复合物选择性减少特定蛋白质的产生3。

Mechanically, siRNA binds to multienzyme complexes of RNA-induced silencing complexes and then localizes to specific sites on mRNA to degrade target mRNA through endonuclease and exonuclease activity4. For example, in diastolic heart failure (DHF) rat models, silencing the SOCS3 gene by administration of adeno-associated virus 9-mediated RNA interference targeting SOCS3 (AAV9-SOCS3 siRNA) significantly reduced myocardial fibrosis and inflammatory responses and improved cardiac function5.

机械地，siRNA与RNA诱导的沉默复合物的多酶复合物结合，然后定位于mRNA上的特定位点，通过核酸内切酶和核酸外切酶活性降解靶mRNA 4。例如，在舒张性心力衰竭（DHF）大鼠模型中，通过施用靶向SOCS3的腺相关病毒9介导的RNA干扰（AAV9-SOCS3 siRNA）沉默SOCS3基因显着降低心肌纤维化和炎症反应并改善心脏功能5。

Therefore, RNA interference (RNAi) has great promise in the treatment of heart failure. miRNA is a compound noncoding RNA molecule with a length of 2.

因此，RNA干扰（RNAi）在心力衰竭的治疗中具有很大的前景。miRNA是一种长度为2的复合非编码RNA分子。

Data availability

数据可用性

Publicly available datasets were analyzed in this study. This data can be found here: Gene Expression Omnibus: GSE59867, GSE9128, GSE134766. Data is provided within the manuscript or supplementary information files.

本研究分析了公开可用的数据集。这些数据可以在这里找到：基因表达综合：GSE59867，GSE9128，GSE134766。数据在手稿或补充信息文件中提供。

AbbreviationsBP:

缩写BP：

Biological process

生物过程

MF:

MF公司：

Molecular function

分子功能

CC:

抄送：

Cellular component

细胞成分

DEGs:

DEG:

Differentially expressed genes

GEO:

地理位置：

Gene Expression Omnibus

KEGG:

KEGG：

Kyoto encyclopedia of genes and genomes

京都基因与基因组百科全书

HF:

高频：

Heart failure

心力衰竭

TF:

TF公司：

Transcription factor

转录因子

PPI:

PPI：

Protein-protein interaction

GPCR:

GPCR：

G-protein coupled receptors

G蛋白偶联受体

FBL:

联邦调查局：

Feedback loop

反馈回路

FFL:

FFL：

Feed-forward loop

前馈回路

ReferencesHanna, F. et al. Epidemiology and long-term outcome in outpatients with chronic heart failure in Northwestern Europe. Heart 105, 1252–1259 (2019).Article

参考文献Hanna，F。等人。西北欧慢性心力衰竭门诊患者的流行病学和长期预后。心脏1051252-1259（2019）。文章

Google Scholar

谷歌学者

Vasan, R. S. et al. Epidemiology of left ventricular systolic dysfunction and heart failure in the framingham study: An echocardiographic study over 3 decades. JACC Cardiovasc. Imaging 11, 1–11 (2018).Article

Vasan，R.S.等人，《framingham研究中左心室收缩功能障碍和心力衰竭的流行病学：30多年的超声心动图研究》。JACC心血管。成像11,1-11（2018）。文章

PubMed

Google Scholar

谷歌学者

Sarzani, R. et al. Molecular therapies in cardiovascular diseases: Small interfering RNA in atherosclerosis, heart failure, and hypertension. Int. J. Mol. Sci. 25(1), 328 (2023).Article

心血管疾病的分子治疗：动脉粥样硬化、心力衰竭和高血压中的小干扰RNA。Int.J.Mol.Sci。25（1），328（2023）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wadhwa, R. et al. Know-how of RNA interference and its applications in research and therapy. Mutat. Res. 567(1), 71–84 (2004).Article

Wadhwa，R.等人。RNA干扰及其在研究和治疗中的应用。突变。第567（1）号决议，第71-84（2004）号决议。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Gao, J. et al. Adeno-associated virus 9-mediated RNA interference targeting SOCS3 alleviates diastolic heart failure in rats. Gene 697, 11–18 (2019).Article

Gao，J。等人。腺相关病毒9介导的靶向SOCS3的RNA干扰减轻了大鼠舒张性心力衰竭。基因697,11-18（2019）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Zhou, H. & Rigoutsos, I. MiR-103a-3p targets the 5′ UTR of GPRC5A in pancreatic cells. RNA 20(9), 1431–1439 (2014).Article

Zhou，H。＆Rigoutsos，I。MiR-103a-3p靶向胰腺细胞中GPRC5A的5'UTR。RNA 20（9），1431–1439（2014）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Elizabeth, S. et al. Osteoclast signaling- targeting miR-146a-3p and miR-155-5p are downregulated in Paget’s disease of bone. Biochim. Biophys. Acta Mol. Basis Dis. 1866, 165852 (2020).Article

Elizabeth，S。等人。破骨细胞信号传导靶向miR-146a-3p和miR-155-5p在佩吉特骨病中下调。生物化学。生物物理。分子基础学报。。文章

Google Scholar

谷歌学者

Chang-Yu, L. et al. FOXO1 and hsa- microRNA-204-5p affect the biologic behavior of MDA-MB-231 breast cancer cells. Int. J. Clin. Exp. Pathol. 13, 1146–1158 (2020).

Chang Yu，L。et al。FOXO1和hsa-microRNA-204-5p影响MDA-MB-231乳腺癌细胞的生物学行为。国际J.临床。。131146-1158（2020）。

Google Scholar

谷歌学者

Yingmin, Lu. et al. Expression profile analysis of circulating microRNAs and their effects on ion channels in Chinese atrial fibrillation patients. Int. J. Clin. Exp. Med. 8, 845–853 (2015).

Yingmin，Lu。等。中国心房颤动患者循环microRNA的表达谱分析及其对离子通道的影响。国际J.临床。实验医学杂志8845-853（2015）。

Google Scholar

谷歌学者

Jiao, J. et al. Characterization of long non-coding RNA and messenger RNA profiles in follicular fluid from mature and immature ovarian follicles of healthy women and women with polycystic ovary syndrome. Hum. Reprod. 33, 1735–1748 (2018).Article

Jiao，J.等人。健康女性和多囊卵巢综合征女性成熟和未成熟卵泡卵泡液中长非编码RNA和信使RNA谱的表征。哼。责备。331735-1748（2018）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Wang, X. et al. MYC-regulated mevalonate metabolism maintains brain tumor-initiating cells. Cancer Res. 77, 4947–4960 (2017).Article

Wang，X。等人。MYC调节的甲羟戊酸代谢维持脑肿瘤起始细胞。癌症研究774947-4960（2017）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Xiaolie, He. et al. Activation of CB2R with AM1241 ameliorates neurodegeneration via the Xist/miR-133b-3p/Pitx3 axis. J. Cell Physiol. 235, 6032–6042 (2020).Article

小烈，他。AM1241激活CB2R可通过Xist/miR-133b-3p/Pitx3轴改善神经变性。J、细胞生理学。2356032–6042（2020）。文章

Google Scholar

谷歌学者

Fariba, K. et al. Bioinformatics prediction and in vitro analysis revealed that miR-17 targets cyclin D1 mRNA in triple negative breast cancer cells. Chem. Biol. Drug Des. 87, 317–320 (2016).Article

生物信息学预测和体外分析显示，miR-17靶向三阴性乳腺癌细胞中的细胞周期蛋白D1 mRNA。化学。。87317-320（2016）。文章

Google Scholar

谷歌学者

Xia Xiaohuan, Lu. et al. miR-106b regulates the proliferation and differentiation of neural stem/progenitor cells through Tp53inp1- Tp53-Cdkn1a axis. Stem Cell Res. Ther. 10, 282 (2019).Article

夏晓欢，陆。等。miR-106b通过Tp53inp1-Tp53-Cdkn1a轴调节神经干/祖细胞的增殖和分化。。10282（2019）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Maciejak, A. et al. Gene expression profiling reveals potential prognostic biomarkers associated with the progression of heart failure. Genome Med. 7(1), 26 (2015).Article

Maciejak，A。等人。基因表达谱揭示了与心力衰竭进展相关的潜在预后生物标志物。基因组医学7（1），26（2015）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Cappuzzello, C. et al. Gene expression profiles in peripheral blood mononuclear cells of chronic heart failure patients. Physiol. Genom. 38(3), 233–240 (2009).Article

Cappuzzello，C.等。慢性心力衰竭患者外周血单个核细胞的基因表达谱。生理学。基因组。38（3），233-240（2009）。文章

CAS

中科院

Google Scholar

谷歌学者

Bain, C. R. et al. DNA methylation patterns from peripheral blood separate coronary artery disease patients with and without heart failure. ESC Heart Fail. 7(5), 2468–2478 (2020).Article

Bain，C.R.等人。外周血DNA甲基化模式将冠心病患者分为心力衰竭患者和非心力衰竭患者。ESC心脏衰竭。7（5），2468–2478（2020）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Smyth, G. K. Limma: linear models for microarray data. In Bioinformatics and Computational Biology Solutions Using R and Bioconductor (eds Gentleman, R. et al.) 397–420 (Springer, Cham, 2005).Chapter

Smyth，G.K.Limma：微阵列数据的线性模型。在使用R和Bioconductor的生物信息学和计算生物学解决方案中（eds Gentleman，R.等人）397-420（Springer，Cham，2005）。第章

Google Scholar

谷歌学者

Robinson Mark, D., McCarthy Davis, J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2010).Article

Robinson-Mark，D.，McCarthy-Davis，J.＆Smyth，G.K.edgeR：用于数字基因表达数据差异表达分析的生物导体软件包。生物信息学26139-140（2010）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Tong, Z. et al. TransmiR v.20: An updated transcription factor-microRNA regulation database. Nucl. Acids Res. 47, D253–D258 (2019).Article

Tong，Z.等人，《TransmiR v.20：更新的转录因子microRNA调控数据库》。核。Acids Res.47，D253–D258（2019）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Vejnar, C. E., Blum, M. & Zdobnov, E. M. miRmap web: Comprehensive microRNA target prediction online. Nucl. Acids Res. 41, W165–W168 (2013).Article

Vejnar，C.E.，Blum，M。＆Zdobnov，E.M。miRmap web：在线综合microRNA靶标预测。核。Acids Res.41，W165–W168（2013）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

John, B. et al. Human MicroRNA targets. PLoS Biol. 2, e363 (2004).Article

John，B.等人。人类MicroRNA靶标。《公共科学图书馆·生物学》。2，e363（2004）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Nathan, W. & Xiaowei, W. miRDB: An online resource for microRNA target prediction and functional annotations. Nucleic Acids Res. 43, D146–D152 (2015).Article

Nathan，W。＆Xiaowei，W。miRDB：microRNA靶标预测和功能注释的在线资源。核酸研究43，D146–D152（2015）。文章

Google Scholar

谷歌学者

Hsu, S. D. et al. miRTarBase: A database curates experimentally validated microRNA-target interactions. Nucl. Acids Res. 39, D163–D169 (2011).Article

Hsu，S.D.等人。miRTarBase：数据库管理实验验证的microRNA-靶标相互作用。核。Acids Res.39，D163–D169（2011）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Luo, Y. et al. New developments on the encyclopedia of DNA elements (ENCODE) data portal. Nucl. Acids Res. 48, D882–D889 (2020).Article

Luo，Y.等人。DNA元素百科全书（ENCODE）数据门户的新发展。核。Acids Res.48，D882–D889（2020）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Paul, S. et al. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498–2504 (2003).Article

Paul，S.等人，《Cytoscape：用于生物分子相互作用网络集成模型的软件环境》。基因组研究132498-2504（2003）。文章

Google Scholar

谷歌学者

Szklarczyk, D. et al. The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucl. Acids Res. 45, D362–D368 (2017).Article

Szklarczyk，D。等人。2017年的STRING数据库：质量控制的蛋白质-蛋白质缔合网络，可广泛访问。核。Acids Res.45，D362–D368（2017）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Tingxin, Z. et al. A protein interaction mechanism for suppressing the mechanosensitive Piezo channels. Nat. Commun. 8(1), 1797 (2017).Article

Tingxin，Z.等人。抑制机械敏感压电通道的蛋白质相互作用机制。国家公社。8（1），1797（2017）。文章

Google Scholar

谷歌学者

Wang, H. et al. Circular RNA TMEM87A promotes cell proliferation and metastasis of gastric cancer by elevating ULK1 via sponging miR-142-5p. J. Gastroenterol. 56(2), 125–138 (2021).Article

Wang，H。等人。环状RNA TMEM87A通过海绵状miR-142-5p升高ULK1来促进胃癌的细胞增殖和转移。J、胃肠道。56（2），125-138（2021）。文章

ADS

CAS

中科院

PubMed

Google Scholar

谷歌学者

Pang, B. et al. Identification of target genes in hypertension and left ventricular remodeling. Medicine 99(28), e21195 (2020).Article

Pang，B.等。高血压和左心室重构靶基因的鉴定。医学99（28），e21195（2020）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kaur, S. et al. Special AT-rich sequence-binding protein 1 (SATB1) functions as an accessory factor in base excision repair. J. Biol. Chem. 291(43), 22769–22780 (2016).Article

Kaur，S。等人。富含AT的特殊序列结合蛋白1（SATB1）在碱基切除修复中起辅助因子的作用。J、生物。化学。291（43），22769-22780（2016）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Panicker, N. et al. Ppp2r2a knockout mice reveal that protein phosphatase 2A regulatory subunit, PP2A-B55α, is an essential regulator of neuronal and epidermal embryonic development. Front. Cell Dev. Biol. 8, 358 (2020).Article

Panicker，N。等人Ppp2r2a基因敲除小鼠揭示了蛋白磷酸酶2A调节亚基PP2A-B55α是神经元和表皮胚胎发育的重要调节剂。正面。细胞开发生物学。8358（2020）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yanhui, G. et al. Effects of PP2A/Nrf2 on experimental diabetes mellitus-related cardiomyopathy by regulation of autophagy and apoptosis through ROS dependent pathway. Cell Signal 62, 109339 (2019).Article

Yanhui，G。等。PP2A/Nrf2通过ROS依赖性途径调节自噬和凋亡对实验性糖尿病相关性心肌病的影响。细胞信号62109339（2019）。文章

Google Scholar

谷歌学者

Patel, K. P. et al. Neuronal expression of Fos protein in the hypothalamus of rats with heart failure. Brain Res. 865(1), 27–34 (2000).Article

Patel，K.P.等人。心力衰竭大鼠下丘脑Fos蛋白的神经元表达。大脑研究865（1），27-34（2000）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Auger-Messier, M. et al. Unrestrained p38 MAPK activation in Dusp1/4 double-null mice induces cardiomyopathy. Circ. Res. 112(1), 48–56 (2013).Article

Auger-Messier，M。等人。Dusp1/4双无效小鼠中不受限制的p38 MAPK激活诱导心肌病。保监会。第112（1）号决议，第48-56（2013）号决议。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Huang, Y. M. et al. The diagnostic value of circulating microRNAs in heart failure. Exp. Ther. Med. 17(3), 1985–2003 (2019).CAS

Huang，Y.M.等人。循环microRNA在心力衰竭中的诊断价值。实验温度。医学杂志17（3），1985–2003（2019）。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Bonauer, A. et al. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science 324(5935), 1710–1713 (2009).Article

Bonauer，A。等人，MicroRNA-92a控制小鼠缺血组织的血管生成和功能恢复。科学324（5935），1710-1713（2009）。文章

ADS

CAS

中科院

PubMed

Google Scholar

谷歌学者

Angelika, B. et al. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science 324, 1710–1713 (2009).Article

Angelika，B。等人。MicroRNA-92a控制小鼠缺血组织的血管生成和功能恢复。科学3241710-1713（2009）。文章

Google Scholar

谷歌学者

Karagiannis, G. S. et al. Integrative pathway dissection of molecular mechanisms of moxLDL-induced vascular smooth muscle phenotype transformation. BMC Cardiovasc. Disord. 13, 4 (2013).Article

Karagiannis，G.S.等人。moxLDL诱导的血管平滑肌表型转化的分子机制的整合途径解剖。BMC心血管。混乱。13，4（2013）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

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Download referencesAcknowledgementsWe thank all lab members for the helpful discussion.FundingThis study was supported by the National Natural Science Foundation of China (81970342).Author informationAuthor notesThese authors contributed equally: Ziyue Zhang, Ziying Zou and Hui Zhang.Authors and AffiliationsDepartment of Cardiology, Sir Run Run Hospital, Nanjing Medical University, 109 Longmian Road, Nanjing, 211112, Jiangsu, People’s Republic of ChinaZiyue Zhang, Ziying Zou, Hui Zhang & Dai-Min ZhangAuthorsZiyue ZhangView author publicationsYou can also search for this author in.

下载参考文献致谢我们感谢所有实验室成员的有益讨论。资助本研究得到了国家自然科学基金（81970342）的资助。作者信息作者注意到这些作者做出了同样的贡献：Ziyue Zhang，Ziying Zou和Hui Zhang。作者和附属机构南京医科大学润润爵士医院心脏病学系，南京龙棉路109号，江苏211112，中华人民共和国Ziyue Zhang，Ziying Zou，Hui Zhang＆Dai Min Zhang作者Ziyue ZhangView作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarZiying ZouView author publicationsYou can also search for this author in

PubMed谷歌学者Ziying ZouView作者出版物您也可以在

PubMed Google ScholarHui ZhangView author publicationsYou can also search for this author in

PubMed Google ScholarHui ZhangView作者出版物您也可以在

PubMed Google ScholarDai-Min ZhangView author publicationsYou can also search for this author in

PubMed Google ScholarDai Min ZhangView作者出版物您也可以在

PubMed Google ScholarContributionsZ. Y. Z., H. Z., Z. Y. Z. contributed to literature search; D. M. Z. contributed to review design, wrote and revised the manuscript. All authors reviewed the manuscript.Corresponding authorCorrespondence to

PubMed谷歌学术贡献。Y、 Z.，H.Z.，Z.Y.Z.为文献检索做出了贡献；D、 M.Z.为审查设计做出了贡献，撰写并修改了手稿。所有作者都审阅了手稿。对应作者对应

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Reprints and permissionsAbout this articleCite this articleZhang, Z., Zou, Z., Zhang, H. et al. Regulatory network analysis based on integrated miRNA-TF reveals key genes in heart failure.

转载和许可本文引用本文Zhang，Z.，Zou，Z.，Zhang，H。等人。基于整合miRNA TF的调控网络分析揭示了心力衰竭的关键基因。

Sci Rep 14, 13896 (2024). https://doi.org/10.1038/s41598-024-64732-yDownload citationReceived: 28 December 2023Accepted: 12 June 2024Published: 17 June 2024DOI: https://doi.org/10.1038/s41598-024-64732-yShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

科学报告1413896（2024）。https://doi.org/10.1038/s41598-024-64732-yDownload引文接收日期：2023年12月28日接收日期：2024年6月12日发布日期：2024年6月17日OI：https://doi.org/10.1038/s41598-024-64732-yShare本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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KeywordsHeart failureMethylationTranscription factorComprehensive analysismicroRNAs

关键词剪切失败甲基化转录因子综合分析microRNA

Subjects

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CardiologyDiseases

心血管疾病

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