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Published on: June 3, 2018
CircRNA Larp4b/miR-298-5p/Mef2c Regulates Cardiac Hypertrophy Induced by Angiotensin II
Qihai Xie1,2, Xiangdong Xu3, Danqun Xiong3
1Department of Cardiology, the First Affiliated Hospital of Soochow University, Suzhou, China.
Insights
Circular RNA Larp4b (circ_Larp4b) exacerbates cardiac hypertrophy by regulating the microRNA-298-5p/myocyte enhancer factor 2 axis. Downregulating circ_Larp4b may offer a therapeutic strategy for heart failure.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Genetics
Background:
- Cardiac hypertrophy (CH) is a key indicator of heart failure progression.
- Circular RNAs (circRNAs) are implicated in various human diseases.
- The specific role of circ_Larp4b in myocardial hypertrophy remains uninvestigated.
Purpose of the Study:
- To investigate the function of circ_Larp4b in Angiotensin II-induced cardiac hypertrophy.
- To elucidate the molecular mechanism involving circ_Larp4b, microRNA-298-5p, and myocyte enhancer factor 2 (Mef2c) in CH.
Main Methods:
- Established a cell model of CH using Angiotensin II (Ang II) treatment in HL-1 cells.
- Quantified gene expression of circ_Larp4b, miR-298-5p, and Mef2c using qRT-PCR.
- Assessed protein levels of CH markers (ACTN2, β-MHC, ANP) and Mef2c via Western blot.
- Validated molecular interactions using dual-luciferase reporter and RNA pull-down assays.
Main Results:
- Circ_Larp4b and Mef2c expression were elevated in Ang II-treated HL-1 cells.
- Downregulation of circ_Larp4b attenuated Ang II-induced CH.
- Circ_Larp4b acts as a sponge for miR-298-5p, which in turn targets Mef2c.
- Overexpression of Mef2c counteracted the effects of miR-298-5p on cell size in the CH model.
Conclusions:
- Circ_Larp4b promotes cardiac hypertrophy by modulating the miR-298-5p/Mef2c pathway.
- Circ_Larp4b represents a potential therapeutic target for managing cardiac hypertrophy and heart failure.
Abstract:
Cardiac hypertrophy (CH) is an early marker in the clinical course of heart failure. Circular RNAs (circRNAs) play important roles in human disease. However, the role of circ_Larp4b in myocardial hypertrophy has not been studied. Angiotensin II (Ang II) treated HL-1 cells to induce a CH cell model. Quantitative real-time polymerase chain reaction was used to detect the expression of circ_Larp4b, microRNA-298-5p, and myocyte enhancer factor 2 (Mef2c). Western blot detected the protein level of alpha-actinin-2 (ACTN2), beta-myosin heavy chain (β-MHC), atrial natriuretic peptide (ANP), and Mef2c. The relationship between miR-298-5p and circ_Larp4b or Mef2c was verified by dual-luciferase reporter assay and RNA pull-down assay. Circ_Larp4b and Mef2c were upregulated in HL-1 cells treated with Ang II. Moreover, circ_Larp4b down-regulation regulated the progress of CH induced by Ang II. MiR-298-5p was a target of circ_Larp4b, and Mef2c was a target of miR-298-5p. Overexpressed Mef2c reversed the cell size inhibited by miR-298-5p in Ang II-induced HL-1 cells. Circ_Larp4b regulated CH progress by regulating miR-298-5p/Mef2c axis.
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