RESUMEN
MiRNAs can be used as promising diagnostic biomarkers of heart failure, while lncRNAs act as competing endogenous RNAs of miRNAs. In this study, we collected peripheral blood monocytes from subjects with or without HF to explore the association between certain lncRNAs, miRNAs and HF. Heart failure patients with preserved or reduced ejection fraction were recruited for investigation. ROC analysis was carried out to evaluate the diagnostic values of certain miRNAs and lncRNAs in HF. Luciferase assays were used to study the regulatory relationship between above miRNAs and lncRNAs. LncRNA overexpression was used to explore the effect of certain miRNAs in H9C2 cells. Expression of miR-30c was significantly decreased in the plasma and peripheral blood monocytes of patients suffering from heart failure, especially in these with reduced ejection fraction. On the contrary, the expression of lncRNA-CASC7 was remarkably increased in the plasma and peripheral blood monocytes of patients suffering from heart failure. Both miR-30c and lncRNA-CASC7 expression showed a promising efficiency as diagnostic biomarkers of heart failure. Luciferase assays indicated that miR-30c played an inhibitory role in lncRNA-CASC7 and IL-11 mRNA expression. Moreover, the overexpression of lncRNA-CASC7 suppressed the expression of miR-30c while evidently increasing the expression of IL-11 mRNA and protein in H9C2 cells. This study clarified the relationship among miR-30c, lncRNA-CASC7 and IL-11 expression and the risk of heart failure and showed that lncRNA-CASC7 is potentially involved in the pathogenesis of HF via modulating the expression of miR-30c.
Asunto(s)
Regulación de la Expresión Génica , Insuficiencia Cardíaca/genética , MicroARNs/genética , ARN Largo no Codificante/metabolismo , Anciano , Animales , Secuencia de Bases , Biomarcadores/sangre , Línea Celular , Regulación hacia Abajo/genética , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/patología , Humanos , Interleucina-11/metabolismo , Masculino , MicroARNs/sangre , MicroARNs/metabolismo , Monocitos/metabolismo , ARN Largo no Codificante/genética , Curva ROC , Ratas , Regulación hacia Arriba/genéticaRESUMEN
Background: Studies have shown that percutaneous coronary intervention (PCI) is considered as the essential therapeutic strategy for the patients with ST-segment elevation myocardial infarction (STEMI). However; no-reflow could still occur in a few patients after PCI. Studies have reported that biomarkers related to no-reflow pathogenetic components could play a prognostic role in the prediction phenomenon. Hence, this study explored the establishment of nomogram model for predicting the occurrence of no-reflow phenomenon after PCI using the lncRNA TUG1/miR-30e/NPPB biomarkers in patients with STEMI after PCI. Methods: In this observational study, a total of 76 STEMI patients who underwent emergency PCI between January 2018 and December 2021were included. The patients after PCI, were divided into reflow (n=44) and no-reflow groups (n=32). The demographic, environmental and clinical risk factors were assessed and analysed between the groups. Quantitative RT-PCR was used to detect TUG1, miR-30e, and NPPB messenger RNA (mRNA) expression levels in the plasma of patients after PCI. Bioinformatic methods were used to predict the interaction of the plasma TUG1/miR-30e/NPPB axis. The risk factors in the no-reflow group were screened using a logistic-regression analysis, and a nomogram prediction model was constructed and validated. Subsequently, a gene set enrichment analysis revealed the function of lncRNA TUG1. Results: Plasma lncRNA TUG1 and NPPB were more highly expressed and miR-30e was more lowly expressed in the no-reflow group than the normal-reflow group (P<0.001). A negative correlation was observed between lncRNA TUG1 and miR-30e, and between miR-30e and NPPB. However, a positive correlation was observed between lncRNA TUG1 and NPPB mRNA. The bioinformatics analysis predicted multiple binding sites on the lncRNA TUG1 and miR-30e. LncRNA TUG1 [odds ratio (OR): 0.163, 95% confidence interval (CI): 0.021-0.944] and hs-CRP (OR: 2.151, 95% CI: 1.536-3.974) found to be as independent predictors. The C-index of this prediction model was 0.982 (95% CI: 0.956-1.000). Conclusions: TUG1 could function as an effective biomarker for no-reflow among patients with STEMI after PCT and the proposed nomogram may provide information for individualized treatment in patients with STEMI.