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Integrated analysis of miRNA-mRNA regulatory network and functional verification of miR-338-3p in coronary heart disease

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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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No data are available.

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

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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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Authors

Contributions

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.

Corresponding author

Correspondence to Chaofeng Sun.

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Statement of ethics

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.

Conflict of interest

The authors declare no competing interests.

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Supplementary information

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Supplementary file1 (JPG 1543 KB) Supplementary Fig. 1. Overall process of this study

10142_2022_941_MOESM2_ESM.xlsx

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

Supplementary file3 (DOCX 16 KB)

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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

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