Abstract
Coronary heart disease is a cardiovascular disease with high morbidity and mortality. Although great progress has been made in treatment, the prognosis is still very poor. Therefore, this project aims to screen potential diagnostic markers and therapeutic targets related to the progression of coronary heart disease. A total of 94 overlapping differentially expressed mRNAs and 70 differentially expressed miRNAs were identified from GSE20681, GSE12288, GSE49823, and GSE105449. Through a series of bioinformatics methods and experiment, we obtained 5 core miRNA-mRNA regulatory pairs, and selected miR-338-3p/RPS23 for functional analysis. Moreover, we found that RPS23 directly targets miR-338-3p by dual luciferase assay, western, and qPCR. And the expression of miR-338-3p and RPS23 is negatively correlated. The AUC value of miR-338-3p is 0.847. Downregulation of miR-338-3p can significantly inhibit the proliferation and migration of HUVEC. On the contrary, overexpression of miR-338-3p promoted the proliferation and migration of HUVEC. In addition, the interference of RPS23 expression can reverse the regulation of miR-338-3p on HUVEC proliferation. In conclusion, miR-338-3p/RPS23 may be involved in the progression of coronary heart disease, and miR-338-3p may be a diagnostic biomarker and therapeutic target for coronary heart disease.
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Abbreviations
- miRNA:
-
MicroRNA
- mRNA:
-
Messenger RNA
- HUVEC:
-
Human umbilical vein endothelial cell
- GEO:
-
Gene Expression Omnibus
- GO:
-
Gene Ontology
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- PPI:
-
Protein-protein interaction
- qPCR:
-
Quantitative polymerase chain reaction
- AUC:
-
Area under the curve
- TCGA:
-
The Cancer Genome Atlas
- WGCNA:
-
Weighted gene co-expression network analysis
- ROC:
-
Receiver operating characteristic
- FC:
-
Fold change
- CCK8:
-
Cell counting kit-8
References
Ali Syeda Z, Langden SSS, Munkhzul C, Lee M, Song SJ (2020) Regulatory mechanism of microRNA expression in cancer. Int J Mol Sci 21:1723. https://doi.org/10.3390/ijms21051723
Caliskan E, de Souza DR, Böning A, Liakopoulos OJ, Choi Y-H, Pepper J et al (2020) Saphenous vein grafts in contemporary coronary artery bypass graft surgery. Nat Rev Cardiol 17:155–169. https://doi.org/10.1038/s41569-019-0249-3
Case BC, Waksman R (2020) Coronary heart disease: have we reached a plateau in primary prevention? J Am Heart Assoc 9:e04963. https://doi.org/10.1161/JAHA.120.016034
Fazmin IT, Achercouk Z, Edling CE, Said A, Jeevaratnam K (2020) Circulating microRNA as a biomarker for coronary artery disease. Biomolecules 10:1354. https://doi.org/10.3390/biom10101354
Hong Y, Chen X, Liang Z, Xu Z, Li Y, Pan Y (2020) MiR-338-3p inhibits cell migration and invasion in human hypopharyngeal cancer via downregulation of ADAM17. Anticancer Drugs 31:925–931. https://doi.org/10.1097/CAD.0000000000000919
Hutter C, Zenklusen JC (2018) The Cancer Genome Atlas: creating lasting value beyond its data. Cell 173:283–285. https://doi.org/10.1016/j.cell.2018.03.042
Infante T, Del Viscovo L, De Rimini ML, Padula S, Caso P, Napoli C (2020) Network medicine: a clinical approach for precision medicine and personalized therapy in coronary heart disease. J Atheroscler Thromb 27:279–302. https://doi.org/10.5551/jat.52407
Katz MJ, Acevedo JM, Wappner P (2014) Growing with the wind. Ribosomal protein hydroxylation and cell growth. Fly (austin) 8:153–156. https://doi.org/10.4161/fly.29943
Li J-H, Liu S, Zhou H et al (2014) starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res 42:D92–D97. https://doi.org/10.1093/nar/gkt1248
Li L-L, Mao C-D, Wang G-P et al (2020) MiR-145–5p alleviates hypoxia/reoxygenation- induced cardiac microvascular endothelial cell injury in coronary heart disease by inhibiting Smad4 expression. Eur Rev Med Pharmacol Sci 24:5008–5017. https://doi.org/10.26355/eurrev_202005_21192
Liang B, Xiang Y, Zhang X, Wang C, Jin B, Zhao Y et al (2020) Systematic pharmacology and GEO database mining revealed the therapeutic mechanism of xuefu zhuyu decoration for atherosclerosis cardiovascular disease. Front Cardiovasc Med 7:592201. https://doi.org/10.3389/fcvm.2020.592201
Lin J, Jiang J, Zhou R, Li X, Ye J (2019) MicroRNA-451b participates in coronary heart disease by targeting VEGFA. Open Med (wars) 15:1–7. https://doi.org/10.1515/med-2020-0001
Malakar AK, Choudhury D, Halder B, Paul P, Uddin A, Chakraborty S (2019) A review on coronary artery disease, its risk factors, and therapeutics. J Cell Physiol 234:16812–16823. https://doi.org/10.1002/jcp.28350
Pelliccia F, Pasceri V, Moretti A, Tanzilli G, Speciale G, Gaudio C (2020) Endothelial progenitor cells predict long-term outcome in patients with coronary artery disease: ten-year follow-up of the PROCREATION extended study. Int J Cardiol 318:123–125. https://doi.org/10.1016/j.ijcard.2020.06.002
Pu X, Chan K, Yang W, Xiao Q, Zhang L, Moore AD et al (2020) Effect of a coronary-heart-disease-associated variant of ADAMTS7 on endothelial cell angiogenesis. Atherosclerosis 296:11–17. https://doi.org/10.1016/j.atherosclerosis.2020.01.015
Rangel-Zuñiga OA, Vals-Delgado C, Alcala-Diaz JF, Quintana-Navarro GM, Krylova Y, Leon-Acuña A et al (2020) A set of miRNAs predicts T2DM remission in patients with coronary heart disease: from the CORDIOPREV study. Mol Ther Nucleic Acids 23:255–263. https://doi.org/10.1016/j.omtn.2020.11.001
Rhee S, Chung JI, King DA, D’amato G, Paik DT, Duan A et al (2018) Endothelial deletion of Ino80 disrupts coronary angiogenesis and causes congenital heart disease. Nat Commun 9:368. https://doi.org/10.1038/s41467-017-02796-3
Ritchie ME, Phipson B, Wu D et al (2015) limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43:e47. https://doi.org/10.1093/nar/gkv007
Shen W, Song Z, Zhong X et al (2022) Sangerbox: a comprehensive, interaction-friendly clinical bioinformatics analysis platform. iMeta 1(3):e36. https://doi.org/10.1002/imt2.36
Sherman BT, Hao M, Qiu J et al (2022) DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res 50:gkac194. https://doi.org/10.1093/nar/gkac194
Sun F, Yu M, Yu J, Liu Z, Zhou X, Liu Y et al (2018) miR-338-3p functions as a tumor suppressor in gastric cancer by targeting PTP1B. Cell Death Dis 9:522. https://doi.org/10.1038/s41419-018-0611-0
Suzuki A, Horie T, Numabe Y (2019) Investigation of molecular biomarker candidates for diagnosis and prognosis of chronic periodontitis by bioinformatics analysis of pooled microarray gene expression datasets in Gene Expression Omnibus (GEO). BMC Oral Health 19:52. https://doi.org/10.1186/s12903-019-0738-0
Szklarczyk D, Gable AL, Nastou KC et al (2021) The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res 49:D605–D612. https://doi.org/10.1093/nar/gkaa1074
Toro-Domínguez D, Martorell-Marugán J, López-Domínguez R, García-Moreno A, González-Rumayor V, Alarcón-Riquelme ME et al (2019) ImaGEO: integrative gene expression meta-analysis from GEO database. Bioinformatics 35:880–882. https://doi.org/10.1093/bioinformatics/bty721
Wang T, Hou Y, Ding X, Song B, Wang F, Hou W (2013) Overexpression, purification, molecular characterization and pharmacological evaluation for anticancer activity of ribosomal protein S23 from the giant panda (Ailuropoda melanoleuca). Mol Med Rep 7:1875–1882. https://doi.org/10.3892/mmr.2013.1430
Wang Z-Y, Zhao T, Zhou J, Gao F (2021) Elevated serum miR-3129-5p contributes to the progression of coronary heart disease via targeting mTOR. Kaohsiung J Med Sci 37:314–323. https://doi.org/10.1002/kjm2.12333
Xie T, Pei Y, Shan P et al (2022) Identification of miRNA-mRNA pairs in the Alzheimer’s disease expression profile and explore the effect of miR-26a-5p/PTGS2 on amyloid-β induced neurotoxicity in Alzheimer’s disease cell model. Front Aging Neurosci 14:909222. https://doi.org/10.3389/fnagi.2022.909222
Yin J, Hou X, Yang S (2019) microRNA-338-3p promotes ox-LDL-induced endothelial cell injury through targeting BAMBI and activating TGF-β/Smad pathway. J Cell Physiol 234:11577–11586. https://doi.org/10.1002/jcp.27814
Yu Y, Yan R, Chen X, Sun T, Yan J (2020) Paeonol suppresses the effect of ox-LDL on mice vascular endothelial cells by regulating miR-338-3p/TET2 axis in atherosclerosis. Mol Cell Biochem 475:127–135. https://doi.org/10.1007/s11010-020-03865-w
Yubero-Serrano EM, Fernandez-Gandara C, Garcia-Rios A, Rangel-Zuñiga OA, Gutierrez-Mariscal FM, Torres-Peña JD et al (2020) Mediterranean diet and endothelial function in patients with coronary heart disease: an analysis of the CORDIOPREV randomized controlled trial. PLoS Med 17:e1003282. https://doi.org/10.1371/journal.pmed.1003282
Zhang T, Liu W, Zeng X-C, Jiang N, Fu B-S, Guo Y et al (2016) Down-regulation of microRNA-338-3p promoted angiogenesis in hepatocellular carcinoma. Biomed Pharmacother 84:583–591. https://doi.org/10.1016/j.biopha.2016.09.056
Zhao B, Wang D, Liu Y, Zhang X, Wan Z, Wang J et al (2020) Six-gene signature associated with immune cells in the progression of atherosclerosis discovered by comprehensive bioinformatics analyses. Cardiovasc Ther 2020:1230513. https://doi.org/10.1155/2020/1230513
Zheng R, Liu Y, Hao Z, Liao H, Xiao C (2020) Clinical characteristics and prognosis of young patients with coronary heart disease. Med Sci Monit 26:e922957. https://doi.org/10.12659/MSM.922957
Zhou Y, Zhou B, Pache L et al (2019) Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 10:1523. https://doi.org/10.1038/s41467-019-09234-6
Zhu Y, Yang T, Duan J, Mu N, Zhang T (2019) MALAT1/miR-15b-5p/MAPK1 mediates endothelial progenitor cells autophagy and affects coronary atherosclerotic heart disease via mTOR signaling pathway. Aging (albany NY) 11:1089–1109. https://doi.org/10.18632/aging.101766
Acknowledgements
We thank the platform of Shanghai Ordovician Biotechnology Co., LTD.
Funding
This work was supported by The Science and Technology Project of Shaanxi Province (2022SF-152); Scientific and Technological Talents Support Program of Shaanxi Provincial People’s Hospital (2022JY-69); Science and Technology Development Incubation Fund Project of Shaanxi Provincial People’s Hospital in 2022 (2022YJY-53).
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QJ is responsible for the plan and design, participates in the acquisition of data, and participates in the drafting of the article. HWQ, ZNE, and GQL analyzed and interpreted the data, and modified important knowledge content. SCF finalized and approved the version to be released and agreed to be responsible for all aspects of the work.
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The study was approved by the ethics committee of First Affiliated Hospital of Xi’an Jiao Tong University, and written informed consent was obtained from all enrolled patients before participation.
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Supplementary file2 (XLSX 12 KB) Supplementary Material 1. Information of 15 peripheral bloods of patients with coronary heart disease and 15 peripheral bloods of healthy control
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Qi, J., Han, W., Zhong, N. et al. Integrated analysis of miRNA-mRNA regulatory network and functional verification of miR-338-3p in coronary heart disease. Funct Integr Genomics 23, 16 (2023). https://doi.org/10.1007/s10142-022-00941-w
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DOI: https://doi.org/10.1007/s10142-022-00941-w