- Title
- Abnormal microRNA expression in cardiac hypertrophy and the regulation of the Endog gene
- Creator
- Quarrell, Sean; Marques, Francine; Jayaswal, Vivek; Curl, Claire; Nankervis, Scott; Yang, Jean; Delbridge, Lea; Harrap, Stephen; Charchar, Fadi
- Date
- 2012
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/64749
- Identifier
- vital:4790
- Identifier
-
https://doi.org/10.1016/j.hlc.2012.05.025
- Identifier
- ISSN:1443-9506
- Abstract
- A deficiency in the gene for endonuclease G (Endog) was recently described as a genetic determinant of cardiac hypertrophy. The mechanisms involved in the regulation of Endog, however, are still to be elucidated. Therefore we hypothesised that Endog, being regulated by small regulatory non-coding RNAs called microRNAs (miRNAs), could contribute to the cardiac hypertrophy of the Hypertrophic Heart Rat (HHR), a human polygenic model of cardiac hypertrophy. From birth the HHR has less and smaller cardiomyocytes, which leads to hypertrophy and cardiac failure later in life. In this study, we examined genome-wide miRNA expression by Agilent Rat miRNA Microarray Kit Release 16.0 and Endog mRNA levels by real-time PCR in the left ventricle of neonatal HHR compared to age-matched rats from its authentic control, the Normal Heart Rat (NHR). Endog mRNA was significantly under-expressed in the HHR (fold change=−4.7; P=0.0001). Sixty-seven miRNAs (FDR P<0.05 and fold change>1.1) were differentially expressed between HHR and NHR (n=16). We then performed an in silico analysis to predict the miRNAs that are able to bind to the 3′ untranslated region of Endog mRNA, and therefore could regulate Endog levels. We discovered that the miRNAs let-7b, miR-338 and miR-347 are predicted to bind to Endog mRNA. Functional studies are being undertaken to determine whether these miRNAs can regulate Endog mRNA levels in vitro and their role in the pathological processes leading to cardiac hypertrophy. These miRNAs could be a new target for the prevention and treatment of cardiac hypertrophy in humans
- Relation
- Heart, Lung and Circulation Vol. 21, no. Supplement 1 (2012), p. s7
- Rights
- Copyright Elsevier
- Rights
- This metadata is freely available under a CCO license
- Subject
- 1102 Cardiorespiratory Medicine and Haematology; 1117 Public Health and Health Services
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