Knockdown of the Long Noncoding RNA ZEB1-AS1 Accelerates Cardiac Hypertrophy via the miR-186-5p/HDAC2 Pathway

Abstract

Background

The role of the long noncoding RNA ZEB1-AS1 in cardiac hypertrophy (CH) remains unclear.

Objectives

To investigate the function of ZEB1-AS1 in the development and progression of CH as well as elucidate its underlying molecular mechanism.

Methods

RNA expression levels were quantified by quantitative real-time PCR. Surface area of AC16 cells was assessed by immunofluorescence staining. Protein expression was evaluated by Western blotting. Interactions among RNAs were examined using luciferase reporter assays and RNA immunoprecipitation. Statistical significance was set at p < 0.05.

Results

The expression of ZEB1-AS1 was upregulated in myocardial tissues and in isoproterenol (ISO)-stimulated AC16 cells. The knockdown of ZEB1-AS1 mitigated ISO-induced hypertrophic responses. Mechanistically, ZEB1-AS1 modulated histone deacetylase 2 (HDAC2) expression by acting as a molecular sponge for miR-186-5p. Consistently, the knockdown of ZEB1-AS1 reduced HDAC2 and decreased the expression of hypertrophic markers, including B-type natriuretic peptide, atrial natriuretic peptide, and β-myosin heavy chain, thereby restraining the progression of CH.

Conclusions

ZEB1-AS1 is upregulated in myocardial tissues and ISO-stimulated AC16 cells. Our findings indicate the ZEB1-AS1/miR-186-5p/HDAC2 axis contributes to CH, providing a mechanistic basis and potential therapeutic target for clinical intervention.