Upregulation of serum miR-4429 discriminates chronic heart failure patients and regulates cardiomyocyte injury via modulating HAPLN1.

Abstract

Chronic heart failure (CHF) is the outcome of various cardiac diseases. Due to the unobvious symptoms of early-stage CHF, the screening of CHF remains a challenging problem. This study focused on the dysregulated miR-4429 and evaluated its significance in the diagnosis and development of CHF, aiming to explore a novel biomarker for CHF. A total of 103 CHF patients and 71 healthy individuals with matched clinicopathological features were enrolled. Serum miR-4429 levels were analyzed by PCR and its significance in discriminating CHF patients was evaluated by receiver operatinf curve (ROC). Cardiomyocyte was treated with H<inf>2</inf>O<inf>2</inf> to mimic cell injury during CHF, the regulatory effect and the underlying mechanism of miR-4429 was investigated by cell transfection and cell counting kit-8 assay. miR-4429 was significantly upregulated in CHF patients (P< 0.0001), which sensitively and specifically discriminated CHF patients from healthy individuals (AUC=0.803, 95% CI=0.735-0.872). miR-4429 was closely associated with the decreased cardiac function of CHF patients (r>0.5, P<0.0001). H<inf>2</inf>O<inf>2</inf> induced increased miR-4429 and reduced HAPLN1 in cardiomyocytes (P<0.001). H<inf>2</inf>O<inf>2</inf>-treated cardiomyocytes showed inhibited proliferation and increased reactive oxygen species (ROS) levels, and silencing miR-4429 could alleviate cardiomyocyte injury caused by H<inf>2</inf>O<inf>2</inf> (P<0.0001). miR-4429 negatively regulated HAPLN1, and the knockdown of HAPLN1 could reverse the protective effect of silencing miR-4429 on cardiomyocyte injury (P<0.0001). The upregulation of miR-4429 served as a biomarker discriminating CHF patients and indicating severe disease conditions. Silencing miR-4429 could alleviate cardiomyocyte injury via negatively regulating HAPLN1.