Weighted Gene Co-expression Network Analysis to Identify Key Modules and Hub Genes Related to Hyperlipidaemia

Overview

Journal Nutr Metab (Lond)

Publisher Biomed Central

Date 2021 Mar 5

PMID 33663541

Citations 2

Authors

Fu-Jun Liao

Peng-Fei Zheng

Yao-Zong Guan

Hong-Wei Pan

Wei Li

Affiliations

Soon will be listed here.

Abstract

Background: The purpose of this study was to explore the potential molecular targets of hyperlipidaemia and the related molecular mechanisms.

Methods: The microarray dataset of GSE66676 obtained from patients with hyperlipidaemia was downloaded. Weighted gene co-expression network (WGCNA) analysis was used to analyse the gene expression profile, and the royal blue module was considered to have the highest correlation. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were implemented for the identification of genes in the royal blue module using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool (version 6.8; http://david.abcc.ncifcrf.gov ). A protein-protein interaction (PPI) network was established by using the online STRING tool. Then, several hub genes were identified by the MCODE and cytoHubba plug-ins in Cytoscape software.

Results: The significant module (royal blue) identified was associated with TC, TG and non-HDL-C. GO and KEGG enrichment analyses revealed that the genes in the royal blue module were associated with carbon metabolism, steroid biosynthesis, fatty acid metabolism and biosynthesis pathways of unsaturated fatty acids. SQLE (degree = 17) was revealed as a key molecule associated with hypercholesterolaemia (HCH), and SCD was revealed as a key molecule associated with hypertriglyceridaemia (HTG). RT-qPCR analysis also confirmed the above results based on our HCH/HTG samples.

Conclusions: SQLE and SCD are related to hyperlipidaemia, and SQLE/SCD may be new targets for cholesterol-lowering or triglyceride-lowering therapy, respectively.

Citing Articles

The interaction between polyphyllin I and SQLE protein induces hepatotoxicity through SREBP-2/HMGCR/SQLE/LSS pathway.

Li Z, Fan Q, Chen M, Dong Y, Li F, Wang M J Pharm Anal. 2023; 13(1):39-54.

PMID: 36820075 PMC: 9937801. DOI: 10.1016/j.jpha.2022.11.005.

Identification of key sex-specific pathways and genes in the subcutaneous adipose tissue from pigs using WGCNA method.

Wang H, Wang X, Li M, Wang S, Chen Q, Lu S BMC Genom Data. 2022; 23(1):35.

PMID: 35538407 PMC: 9086418. DOI: 10.1186/s12863-022-01054-w.

References

Can M, Acikgoz S, Mungan G, Ugurbas E, Ankarali H, Sumbuloglu V . Is direct method of low density lipoprotein cholesterol measurement appropriate for targeting lipid lowering therapy?. Int J Cardiol. 2009; 142(1):105-7. DOI: 10.1016/j.ijcard.2008.11.141. View

Castellano-Castillo D, Moreno-Indias I, Sanchez-Alcoholado L, Ramos-Molina B, Alcaide-Torres J, Morcillo S . Altered Adipose Tissue DNA Methylation Status in Metabolic Syndrome: Relationships Between Global DNA Methylation and Specific Methylation at Adipogenic, Lipid Metabolism and Inflammatory Candidate Genes and Metabolic Variables. J Clin Med. 2019; 8(1). PMC: 6352101. DOI: 10.3390/jcm8010087. View

Hidaka Y, Satoh T, Kamei T . Regulation of squalene epoxidase in HepG2 cells. J Lipid Res. 1990; 31(11):2087-94. View

Khounphinith E, Yin R, Cao X, Huang F, Wu J, Li H . rs6882076 SNP Is Associated with Decreased Levels of Triglycerides and the Risk of Coronary Heart Disease and Ischemic Stroke. Int J Med Sci. 2019; 16(6):864-871. PMC: 6643107. DOI: 10.7150/ijms.31729. View

Alberti K, Zimmet P . Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998; 15(7):539-53. DOI: 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S. 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

Zheng P, Yin R, Liu C, Deng G, Guan Y, Wei B . SYNE1-QK1 SNPs, G × G and G × E interactions on the risk of hyperlipidaemia. J Cell Mol Med. 2020; 24(10):5772-5785. PMC: 7214174. DOI: 10.1111/jcmm.15239. View

Herman-Edelstein M, Scherzer P, Tobar A, Levi M, Gafter U . Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy. J Lipid Res. 2013; 55(3):561-72. PMC: 3934740. DOI: 10.1194/jlr.P040501. View

Pai J, Mukamal K, Rimm E . Long-term alcohol consumption in relation to all-cause and cardiovascular mortality among survivors of myocardial infarction: the Health Professionals Follow-up Study. Eur Heart J. 2012; 33(13):1598-605. PMC: 3388015. DOI: 10.1093/eurheartj/ehs047. View

10.

Pearce N, YATES J, Berkhout T, Jackson B, Tew D, Boyd H . The role of ATP citrate-lyase in the metabolic regulation of plasma lipids. Hypolipidaemic effects of SB-204990, a lactone prodrug of the potent ATP citrate-lyase inhibitor SB-201076. Biochem J. 1998; 334 ( Pt 1):113-9. PMC: 1219669. DOI: 10.1042/bj3340113. View

11.

Smoot M, Ono K, Ruscheinski J, Wang P, Ideker T . Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics. 2010; 27(3):431-2. PMC: 3031041. DOI: 10.1093/bioinformatics/btq675. View

12.

Ruan J, Dean A, Zhang W . A general co-expression network-based approach to gene expression analysis: comparison and applications. BMC Syst Biol. 2010; 4:8. PMC: 2829495. DOI: 10.1186/1752-0509-4-8. View

13.

Gencer B, Koskinas K, Raber L, Karagiannis A, Nanchen D, Auer R . Eligibility for PCSK9 Inhibitors According to American College of Cardiology (ACC) and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) Guidelines After Acute Coronary Syndromes. J Am Heart Assoc. 2017; 6(11). PMC: 5721754. DOI: 10.1161/JAHA.117.006537. View

14.

Honsho M, Abe Y, Fujiki Y . Dysregulation of Plasmalogen Homeostasis Impairs Cholesterol Biosynthesis. J Biol Chem. 2015; 290(48):28822-33. PMC: 4661398. DOI: 10.1074/jbc.M115.656983. View

15.

Grundy S, Cleeman J, Merz C, Brewer Jr H, Clark L, Hunninghake D . Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. J Am Coll Cardiol. 2004; 44(3):720-32. DOI: 10.1016/j.jacc.2004.07.001. View

16.

Ntambi J, Miyazaki M . Regulation of stearoyl-CoA desaturases and role in metabolism. Prog Lipid Res. 2003; 43(2):91-104. DOI: 10.1016/s0163-7827(03)00039-0. View

17.

Stevenson J, Luu W, Kristiana I, Brown A . Squalene mono-oxygenase, a key enzyme in cholesterol synthesis, is stabilized by unsaturated fatty acids. Biochem J. 2014; 461(3):435-42. DOI: 10.1042/BJ20131404. View

18.

Chow C, Jolly S, Rao-Melacini P, Fox K, Anand S, Yusuf S . Association of diet, exercise, and smoking modification with risk of early cardiovascular events after acute coronary syndromes. Circulation. 2010; 121(6):750-8. DOI: 10.1161/CIRCULATIONAHA.109.891523. View

19.

Chin C, Chen S, Wu H, Ho C, Ko M, Lin C . cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014; 8 Suppl 4:S11. PMC: 4290687. DOI: 10.1186/1752-0509-8-S4-S11. View

20.

Ntambi J, Miyazaki M, Stoehr J, Lan H, Kendziorski C, Yandell B . Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proc Natl Acad Sci U S A. 2002; 99(17):11482-6. PMC: 123282. DOI: 10.1073/pnas.132384699. View