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In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
Published on: June 15, 2018
Integrated analysis of miRNA-mRNA regulatory network and functional verification of miR-338-3p in coronary heart
Jie Qi1,2, Wenqi Han1, Nier Zhong1
1Second Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, Xi'an, 710068, People's Republic of China.
Insights
Researchers identified miR-338-3p and RPS23 as key players in coronary heart disease (CHD) progression. MiR-338-3p shows potential as a diagnostic biomarker and therapeutic target for this cardiovascular disease.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Biomarker Discovery
Background:
- Coronary heart disease (CHD) presents significant morbidity and mortality despite treatment advances.
- Prognosis for CHD patients remains poor, necessitating novel diagnostic and therapeutic strategies.
Purpose of the Study:
- To identify potential diagnostic markers and therapeutic targets for coronary heart disease progression.
- To elucidate the role of specific microRNA-messenger RNA (miRNA-mRNA) regulatory pairs in CHD.
Main Methods:
- Bioinformatic analysis of gene expression datasets (GSE20681, GSE12288, GSE49823, GSE105449) to identify differentially expressed mRNAs and miRNAs.
- Selection and validation of core miRNA-mRNA regulatory pairs using dual luciferase assays, Western blotting, and quantitative PCR (qPCR).
- Functional analysis of selected pair (miR-338-3p/RPS23) in human umbilical vein endothelial cells (HUVECs) to assess effects on proliferation and migration.
Main Results:
- Identification of 94 differentially expressed mRNAs and 70 differentially expressed miRNAs, leading to 5 core miRNA-mRNA regulatory pairs.
- miR-338-3p directly targets RPS23, with a negative correlation in their expression.
- miR-338-3p demonstrated diagnostic potential (AUC=0.847) and significantly regulated HUVEC proliferation and migration; RPS23 modulated these effects.
Conclusions:
- The miR-338-3p/RPS23 axis is implicated in the progression of coronary heart disease.
- miR-338-3p emerges as a potential diagnostic biomarker and therapeutic target for CHD.
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.
