Expression and clinical significance of miR-8078 in patients with congenital heart disease-associated pulmonary arterial hypertension

Abstract

Objectives: This study aimed to analyze the plasma levels of miR-8078 in patients with congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) and to explore the diagnostic value and potential mechanisms of miR-8078 in CHD-PAH.

Methods: Plasma samples were collected from 110 patients with congenital heart disease. Subsequently, based on the mean pulmonary artery pressure (PAPm) measured via right heart catheterization, the patients were divided into three groups: no-PAH group (Group W, PAPm < 25 mmHg), mild group (Group M, 25 mmHg ≤ PAPm < 35 mmHg), and moderate-to-severe group (Group H, PAPm ≥ 35 mmHg). The study also involved a control group (Group C) comprised of 40 healthy individuals. The miR-8078 expression levels were determined by means of reverse transcription-polymerase chain reaction (RT-PCR). The target genes and biological functions of miR-8078 were predicted using TargetScan, PicTar, and miRDB software. Statistical analysis was performed to evaluate the correlation between miR-8078 and hemodynamic parameters in CHD-PAH, in addition to its diagnostic value.

Results: The plasma miR-8078 expression levels were significantly higher in the moderate-to-severe group when compared with the control group, no-PAH group, and mild group (p < 0.05). Furthermore, the mild group and no-PAH group showed significantly higher miR-8078 expression levels when compared with the control group (p < 0.05). Both results were consistent with the high-throughput sequencing results. KEGG pathway analysis of the miR-8078 target genes revealed associations with morphine addiction, ubiquitin-mediated proteolysis, and parathyroid hormone synthesis and secretion. GO enrichment analysis indicated the involvement of miR-8078 in the regulation of transcription by RNA polymerase II, the positive regulation of stress-activated MAPK cascade, the transmembrane transport of CI^- and K⁺ ions, chromatin organization, and atrioventricular valve morphogenesis. Correlation analysis showed that the miR-8078 expression levels were positively correlated with the pulmonary artery systolic pressure, mean pulmonary artery pressure, and pulmonary vascular resistance (correlation coefficients of 0.404, 0.397, and 0.283, respectively; all p < 0.05). Univariate and multivariate regression analyses revealed plasma miR-8078 (odds ratio: 1.475, 95 % confidence interval: 1.053-2.065, p < 0.05) to be an independent risk factor for CHD-PAH. Receiver operating characteristic curve analysis revealed that the area under the curve (AUC) for miR-8078 alone and for B-type natriuretic peptide alone in diagnosing CHD-PAH was 0.686 and 0.851, respectively, while the AUC for a combined diagnosis was 0.874, which was higher than that associated with the individual diagnoses (p < 0.05).

Conclusion: The findings of this study suggest that miR-8078 is upregulated in CHD-PAH, while the results of the bioinformatics analysis indicate its involvement in the pathogenesis of CHD-PAH, suggesting it to be a potential therapeutic target or biomarker.

Keywords: Bioinformatics analysis; Circulating microRNA; Congenital heart disease; Pulmonary arterial hypertension; miR-8078.