In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 18, No. 11 ( 2014-11), p. 2266-2274
Abstract:
The molecular mechanisms that drive the development of cardiac hypertrophy in hypertrophic cardiomyopathy ( HCM ) remain elusive. Accumulated evidence suggests that micro RNA s are essential regulators of cardiac remodelling. We have been suggested that micro RNA s could play a role in the process of HCM . To uncover which micro RNA s were changed in their expression, micro RNA microarrays were performed on heart tissue from HCM patients ( n = 7) and from healthy donors ( n = 5). Among the 13 micro RNA s 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 ( TSC 1) was a direct target of miR‐451. Overexpression of miR‐451 in both HeLa cells and NRCM suppressed the expression of TSC 1. Furthermore, TSC 1 was significantly up‐regulated in HCM myocardia, which correlated with the decreased levels of miR‐451. As TSC 1 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 LC 3 and Beclin‐1. Taken together, our findings indicate that miR‐451 regulates cardiac hypertrophy and cardiac autophagy by targeting TSC 1. The down‐regulation of miR‐451 may contribute to the development of HCM and may be a potential therapeutic target for this disease.
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2014.18.issue-11
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2076114-4
