RGD Reference Report - MiR-451 is decreased in hypertrophic cardiomyopathy and regulates autophagy by targeting TSC1. - Rat Genome Database

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MiR-451 is decreased in hypertrophic cardiomyopathy and regulates autophagy by targeting TSC1.

Authors: Song, L  Su, M  Wang, S  Zou, Y  Wang, X  Wang, Y  Cui, H  Zhao, P  Hui, R  Wang, J 
Citation: Song L, etal., J Cell Mol Med. 2014 Nov;18(11):2266-74. doi: 10.1111/jcmm.12380. Epub 2014 Sep 11.
RGD ID: 11558015
Pubmed: PMID:25209900   (View Abstract at PubMed)
PMCID: PMC4224559   (View Article at PubMed Central)
DOI: DOI:10.1111/jcmm.12380   (Journal Full-text)

The molecular mechanisms that drive the development of cardiac hypertrophy in hypertrophic cardiomyopathy (HCM) remain elusive. Accumulated evidence suggests that microRNAs are essential regulators of cardiac remodelling. We have been suggested that microRNAs could play a role in the process of HCM. To uncover which microRNAs were changed in their expression, microRNA microarrays were performed on heart tissue from HCM patients (n = 7) and from healthy donors (n = 5). Among the 13 microRNAs that were differentially expressed in HCM, miR-451 was the most down-regulated. Ectopic overexpression of miR-451 in neonatal rat cardiomyocytes (NRCM) decreased the cell size, whereas knockdown of endogenous miR-451 increased the cell surface area. Luciferase reporter assay analyses demonstrated that tuberous sclerosis complex 1 (TSC1) was a direct target of miR-451. Overexpression of miR-451 in both HeLa cells and NRCM suppressed the expression of TSC1. Furthermore, TSC1 was significantly up-regulated in HCM myocardia, which correlated with the decreased levels of miR-451. As TSC1 is a known positive regulator of autophagy, we examined the role of miR-451 in the regulation of autophagy. Overexpression of miR-451 in vitro inhibited the formation of the autophagosome. Conversely, miR-451 knockdown accelerated autophagosome formation. Consistently, an increased number of autophagosomes was observed in HCM myocardia, accompanied by up-regulated autophagy markers, and the lipidated form of LC3 and Beclin-1. Taken together, our findings indicate that miR-451 regulates cardiac hypertrophy and cardiac autophagy by targeting TSC1. The down-regulation of miR-451 may contribute to the development of HCM and may be a potential therapeutic target for this disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertrophic cardiomyopathy  IEP 11558015protein:decreased expression:heartRGD 
hypertrophic cardiomyopathy  IEP 11558015; 11558015protein:increased expression:heartRGD 
hypertrophic cardiomyopathy  ISOBCL2 (Homo sapiens)11558015; 11558015protein:decreased expression:heartRGD 
hypertrophic cardiomyopathy  ISOBECN1 (Homo sapiens)11558015; 11558015protein:increased expression:heartRGD 
hypertrophic cardiomyopathy  IEP 11558015RNA:decreased expression:heartRGD 
hypertrophic cardiomyopathy  ISOMAP1LC3A (Homo sapiens)11558015; 11558015protein:increased expression:heartRGD 
hypertrophic cardiomyopathy  ISOMIR451A (Homo sapiens)11558015; 11558015RNA:decreased expression:heartRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of cell growth involved in cardiac muscle cell development  IMP 11558015 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bcl2  (BCL2, apoptosis regulator)
Becn1  (beclin 1)
Map1lc3a  (microtubule-associated protein 1 light chain 3 alpha)
Mir451a  (microRNA 451a)

Genes (Mus musculus)
Bcl2  (B cell leukemia/lymphoma 2)
Becn1  (beclin 1, autophagy related)
Map1lc3a  (microtubule-associated protein 1 light chain 3 alpha)
Mir451a  (microRNA 451a)

Genes (Homo sapiens)
BCL2  (BCL2 apoptosis regulator)
BECN1  (beclin 1)
MAP1LC3A  (microtubule associated protein 1 light chain 3 alpha)
MIR451A  (microRNA 451a)


Additional Information