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MiR-466h-5p induces expression of myocardin with complementary promoter sequences
Ying Luo1, Chen Liang1, Yao Xu1
1Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, Hubei, China.
Abstract:
A number of studies microRNAs (miRNA) play an important role in cardiac physiological and pathological processes. In these studies, miRNA regulates gene expression by repressing translation or directing sequence-specific degradation of complementary mRNA. Here, we reveal a new regulatory mechanism in the process of cardiac hypertrophy which miRNA may also regulate the promoter activity of target genes. In the course of the study, we find that miR-466h-5p regulates the occurrence of myocardial hypertrophy via myocardin and it can upregulate the expression of myocardin through directly binding to the promoter region of myocardin. Meanwhile, we also find that myocardin can reverse-activate miR-466h-5p expression through binding to the CarG box. Thus, miR-466h-5p and myocardin form a positive regulation loop in the process of cardiac hypertrophy. These findings reveal a new mode by which miRNAs may regulate gene expression and may play a positive role in revealing the complete mechanisms of cardiac hypertrophy.
Insights
MicroRNAs (miRNA) regulate cardiac hypertrophy by controlling gene expression. This study reveals a novel positive feedback loop between miR-466h-5p and myocardin, crucial for cardiac hypertrophy development.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Epigenetics
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression in cardiac physiology and pathology.
- Existing knowledge indicates miRNAs primarily control translation or mRNA degradation.
- Cardiac hypertrophy involves complex gene regulatory networks.
Purpose of the Study:
- To investigate a novel regulatory mechanism of microRNAs in cardiac hypertrophy.
- To elucidate the role of miR-466h-5p in myocardial hypertrophy.
- To identify the interaction between miR-466h-5p and myocardin in cardiac hypertrophy.
Main Methods:
- Analysis of miRNA and gene expression in cardiac hypertrophy models.
- Luciferase reporter assays to confirm target gene binding.
- Identification of binding sites on gene promoters and regulatory elements.
Main Results:
- miR-466h-5p was found to regulate cardiac hypertrophy.
- miR-466h-5p upregulates myocardin expression by binding to its promoter region.
- Myocardin activates miR-466h-5p expression by binding to the CarG box, forming a positive feedback loop.
Conclusions:
- A novel miRNA-mediated gene regulation mechanism involving promoter activity was identified.
- A positive feedback loop between miR-466h-5p and myocardin contributes to cardiac hypertrophy.
- These findings offer new insights into the molecular mechanisms of cardiac hypertrophy.
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