Work

MiR-1 alleviates chronic heart failure through HCN2/HCN4 axis in vitro

Year: 2025

Type: article

Abstract: OBJECTIVE: Chronic heart failure (CHF) is a complex and progressive condition. This study aimed to investigate the potential regulatory effect of miR-1 on CHF through the hyperpolarization-activated cyclic nucleotide-gated channels 2 and 4 (HCN2/HCN4) axis. METHOD: The expression of miR-1 was examined in individuals diagnosed with CHF. The patients' level of NT-proBNP was evaluated. A cellular model using H9c2 cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) was established. RT-qPCR and western blot were performed to determine the levels of miR-1, HCN2, or HCN4. Elisa was used to measure the levels of TNF-α and IL-6. The potential target of miR-1 on HCN2 and HCN4 was verified using the dual luciferase assay. Overexpression of miR-1 or HCN was employed to explore the specific mechanism of miR-1 and HCN on CHF. The MTT assay was used to evaluate cell viability, while apoptosis was quantified through flow cytometry. RESULTS: In both patients with CHF and OGD/R-treated H9c2 cells, miR-1 levels were found to be reduced. The overexpression of miR-1 notably suppressed the secretion of TNF-α and IL-6 (P < 0.05). Overexpression of miR-1 also markedly increased cell viability (P < 0.01) and reduced apoptosis (P < 0.05) in OGD/R-treated H9c2 cells. Using miRNA-target prediction databases and luciferase reporter assays, we identified HCN2 and HCN4 as direct targets of miR-1. Moreover, overexpression of HCN2 and HCN4 counteracted the protective effects of miR-1, as evidenced by a significant reduction in cell viability (P < 0.01) and an increase in apoptosis (P < 0.05). CONCLUSION: This study suggests that miR-1 regulates cell viability and apoptosis in CHF through the HCN2/HCN4 axis, highlighting its potential as a therapeutic target for CHF.

Source: Tissue and Cell

DOI: 10.1016/j.tice.2025.102921

Authors: Yishan Luo, Wanjie Gu, Zhe Pan, Jun Zeng, Haiyan Yin

Institutions: First Affiliated Hospital of Jinan University, Guangzhou First People's Hospital

Language: English

Topic: MicroRNA in disease regulation

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $2,680