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Author Spotlight: A Computational Pipeline for Analyzing Chimeric Noncoding RNA-Target RNA Interactions in High-Throughput Sequencing Data
Published on: December 1, 2023
Knockdown of the Long Noncoding RNA ZEB1-AS1 Accelerates Cardiac Hypertrophy via the miR-186-5p/HDAC2 Pathway
Bingfeng Cao1, Qingxia Liu2, Xiaoyuan Zhang1
1Department of Cardiology - Weihai Central Hospital, Shandong - China.
Insights
The long noncoding RNA ZEB1-AS1 is elevated in cardiac hypertrophy (CH). It promotes CH by sponging miR-186-5p, increasing histone deacetylase 2 (HDAC2) expression, and is a potential therapeutic target.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Noncoding RNA Biology
Background:
- Cardiac hypertrophy (CH) is a significant cardiovascular condition.
- The role of long noncoding RNA ZEB1-AS1 in CH pathogenesis is not well understood.
Purpose of the Study:
- To investigate the function of ZEB1-AS1 in cardiac hypertrophy development.
- To elucidate the molecular mechanisms underlying ZEB1-AS1's role in CH.
Main Methods:
- Quantitative real-time PCR for RNA expression.
- Immunofluorescence staining for cell surface area.
- Western blotting for protein expression.
- Luciferase reporter assays and RNA immunoprecipitation for RNA interactions.
Main Results:
- ZEB1-AS1 expression is upregulated in myocardial tissues and isoproterenol (ISO)-stimulated cells.
- Knockdown of ZEB1-AS1 reduced ISO-induced hypertrophic responses.
- ZEB1-AS1 acts as a molecular sponge for miR-186-5p, upregulating histone deacetylase 2 (HDAC2) and hypertrophic markers.
Conclusions:
- ZEB1-AS1 is upregulated in CH models.
- The ZEB1-AS1/miR-186-5p/HDAC2 axis is implicated in CH progression.
- ZEB1-AS1 presents a potential therapeutic target for CH.
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.
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