Identification of Key Proteins and LncRNAs in Hypertrophic Cardiomyopathy by Integrated Network Analysis

Overview

Journal Arch Med Sci

Specialty General Medicine

Date 2019 Mar 23

PMID 30899302

Citations 10

Authors

Xiaofeng Hu

Guilin Shen

Xiaoli Lu

Guomin Ding

Lishui Shen

Affiliations

Soon will be listed here.

Abstract

Introduction: Hypertrophic cardiomyopathy (HCM), a genetically heterogeneous disorder of cardiac myocytes, is one of the main causes of sudden cardiac death of young people. However, the molecular mechanism involved in HCM has remained largely unclear. Of note, non-coding RNAs were reported to play an important role in human diseases. In this study, we focused on identifying differentially expressed long non-coding RNA (lncRNAs) and mRNAs in HCM by analyzing a public dataset (GSE36961).

Material And Methods: We performed bioinformatics analysis to explore key pathways underlying HCM progression. Gene Ontology (GO) analysis was first performed to evaluate the potential roles of differentially expressed genes and lncRNAs in HCM. Moreover, protein-protein interaction (PPI) networks were constructed to reveal interactions among differentially expressed proteins. Specifically, co-expression networks were also constructed to identify hub lncRNAs in HCM.

Results: A total of 6147 mRNAs ( < 0.001) and 126 lncRNAs ( < 0.001) were found to be dysregulated in HCM. Gene Ontology (GO) analysis showed that these differentially expressed genes and lncRNAs were associated with metabolism, energy pathways, signal transduction, and cell communication. Moreover, TSPYL3, LOC401431, LOC158376, LOC606724, PDIA3P and LOH3CR2A ( < 0.001) were identified as key lncRNAs in HCM progression.

Conclusions: Taken together, our analysis revealed a series of lncRNAs and mRNAs that were differentially expressed in HCM and which were involved in HCM progression by regulating pathways, such as metabolism, energy pathways, signal transduction, and cell communication. This study will provide useful information to explore the mechanisms underlying HCM progression and to provide potential candidate biomarkers for diagnosis in HCM.

Citing Articles

Analysis of key lncRNA related to Parkinson's disease based on gene co-expression weight networks.

Liang W, Zhao W, Li B, Luo J, Li X, Jia W Neurosciences (Riyadh). 2025; 30(1):20-29.

PMID: 39800420 PMC: 11753585. DOI: 10.17712/nsj.2025.1.20230112.

Downregulated expression of lncRNA TUBA4B predicts unfavorable prognosis and suppresses glioma progression by sponging miR-183 to regulate SMAD4 expression.

Bao X, Wang S, Li Y Arch Med Sci. 2024; 20(3):863-875.

PMID: 39050167 PMC: 11264155. DOI: 10.5114/aoms.2020.92817.

Identification of key genes related to heart failure by analysis of expression profiles.

Wang C, Li Q, Yang H, Gao C, Du Q, Zhang C Arch Med Sci. 2024; 20(2):517-527.

PMID: 38757035 PMC: 11094840. DOI: 10.5114/aoms/114896.

Transcriptomic Analyses and Experimental Validation Identified Immune-Related lncRNA-mRNA Pair - Regulating the Progression of Hypertrophic Cardiomyopathy.

Zhang Y, Zhao J, Jin Q, Zhuang L Int J Mol Sci. 2024; 25(5).

PMID: 38474063 PMC: 10932045. DOI: 10.3390/ijms25052816.

Integrative analysis reveals key mRNA and long non-coding RNA interaction in idiopathic pulmonary arterial hypertension.

Wang R, Zhuang Q, Wang J, Yang M, Zhang X, Shen J Arch Med Sci. 2023; 19(6):1879-1888.

PMID: 38058710 PMC: 10696996. DOI: 10.5114/aoms.2020.96074.

References

Corrado D, Basso C, Thiene G . Sudden cardiac death in young people with apparently normal heart. Cardiovasc Res. 2001; 50(2):399-408. DOI: 10.1016/s0008-6363(01)00254-1. View

Bader G, Hogue C . An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics. 2003; 4:2. PMC: 149346. DOI: 10.1186/1471-2105-4-2. View

Maron M, Olivotto I, Betocchi S, Casey S, Lesser J, Losi M . Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med. 2003; 348(4):295-303. DOI: 10.1056/NEJMoa021332. View

Chung M, Tsoutsman T, Semsarian C . Hypertrophic cardiomyopathy: from gene defect to clinical disease. Cell Res. 2003; 13(1):9-20. DOI: 10.1038/sj.cr.7290146. View

Erdmann J, Daehmlow S, Wischke S, Senyuva M, Werner U, Raible J . Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy. Clin Genet. 2003; 64(4):339-49. DOI: 10.1034/j.1399-0004.2003.00151.x. View

Shannon P, Markiel A, Ozier O, Baliga N, Wang J, Ramage D . Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003; 13(11):2498-504. PMC: 403769. DOI: 10.1101/gr.1239303. View

Harris M, Clark J, Ireland A, Lomax J, Ashburner M, Foulger R . The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res. 2003; 32(Database issue):D258-61. PMC: 308770. DOI: 10.1093/nar/gkh036. View

Assenov Y, Ramirez F, Schelhorn S, Lengauer T, Albrecht M . Computing topological parameters of biological networks. Bioinformatics. 2007; 24(2):282-4. DOI: 10.1093/bioinformatics/btm554. View

Lee H, Chen Q, Wolfram J, Richardson S, Liner A, Siedlak S . Cell cycle re-entry and mitochondrial defects in myc-mediated hypertrophic cardiomyopathy and heart failure. PLoS One. 2009; 4(9):e7172. PMC: 2747003. DOI: 10.1371/journal.pone.0007172. View

10.

Girolami F, Ho C, Semsarian C, Baldi M, Will M, Baldini K . Clinical features and outcome of hypertrophic cardiomyopathy associated with triple sarcomere protein gene mutations. J Am Coll Cardiol. 2010; 55(14):1444-53. DOI: 10.1016/j.jacc.2009.11.062. View

11.

Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P . The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 2010; 39(Database issue):D561-8. PMC: 3013807. DOI: 10.1093/nar/gkq973. View

12.

Ashrafian H, McKenna W, Watkins H . Disease pathways and novel therapeutic targets in hypertrophic cardiomyopathy. Circ Res. 2011; 109(1):86-96. DOI: 10.1161/CIRCRESAHA.111.242974. View

13.

Wolfram J, Lesnefsky E, Hoit B, Smith M, Lee H . Therapeutic potential of c-Myc inhibition in the treatment of hypertrophic cardiomyopathy. Ther Adv Chronic Dis. 2011; 2(2):133-44. PMC: 3156459. DOI: 10.1177/2040622310393059. View

14.

Zhang X, Sun S, Pu J, Tsang A, Lee D, Man V . Long non-coding RNA expression profiles predict clinical phenotypes in glioma. Neurobiol Dis. 2012; 48(1):1-8. DOI: 10.1016/j.nbd.2012.06.004. View

15.

Kornienko A, Guenzl P, Barlow D, Pauler F . Gene regulation by the act of long non-coding RNA transcription. BMC Biol. 2013; 11:59. PMC: 3668284. DOI: 10.1186/1741-7007-11-59. View

16.

Shi X, Sun M, Liu H, Yao Y, Song Y . Long non-coding RNAs: a new frontier in the study of human diseases. Cancer Lett. 2013; 339(2):159-66. DOI: 10.1016/j.canlet.2013.06.013. View

17.

Suresh R, Li X, Chiriac A, Goel K, Terzic A, Perez-Terzic C . Transcriptome from circulating cells suggests dysregulated pathways associated with long-term recurrent events following first-time myocardial infarction. J Mol Cell Cardiol. 2014; 74:13-21. PMC: 4115027. DOI: 10.1016/j.yjmcc.2014.04.017. View

18.

Wang P, Mao B, Luo W, Wei B, Jiang W, Liu D . The alteration of Hippo/YAP signaling in the development of hypertrophic cardiomyopathy. Basic Res Cardiol. 2014; 109(5):435. DOI: 10.1007/s00395-014-0435-8. View

19.

Baertling F, van den Brand M, Hertecant J, Al-Shamsi A, van den Heuvel L, Distelmaier F . Mutations in COA6 cause cytochrome c oxidase deficiency and neonatal hypertrophic cardiomyopathy. Hum Mutat. 2014; 36(1):34-8. DOI: 10.1002/humu.22715. View

20.

Yang W, Li Y, He F, Wu H . Microarray profiling of long non-coding RNA (lncRNA) associated with hypertrophic cardiomyopathy. BMC Cardiovasc Disord. 2015; 15:62. PMC: 4490660. DOI: 10.1186/s12872-015-0056-7. View