miR-106a promotes cardiac hypertrophy by targeting mitofusin 2

Guan, Xiaoxiang; Wang, Lu; Liu, Zhen-hong; Guo, Xiaofei; Jiang, Yuan; Lu, Ying; Peng, Yanli; Liu, Tianhua; Yang, Baofeng; Shan, Hongli; Zhang, Yong; Xu, Chaoqian

doi:10.1016/j.yjmcc.2016.08.016

Cited by 64 publications

(63 citation statements)

References 51 publications

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“…Thus, it provides new evidences to explore the functions of miRNAs in modulating mitochondrial function. For instance, miR‐106a accelerates cardiac hypertrophy via restraining mitofusin 2, miR‐497 and miR‐485‐5p attenuate cardiac hypertrophy by targeting Sirt4 and MAPL, respectively . In present study, we found that miRNA‐miR‐376b‐3p negatively regulate mitochondrial fission in cardiac hypertrophic NRVCs by targeting MFF.…”

Section: Discussionsupporting

confidence: 55%

miR‐376b‐3p attenuates mitochondrial fission and cardiac hypertrophy by targeting mitochondrial fission factor

Sun

Yang

et al. 2018

Clin Exp Pharma Physio

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Mitochondrial dysfunction contributes to the pathogenesis of cardiac hypertrophy. The disequilibrium of mitochondrial dynamic, which refers to mitochondrial fusion and fission, leads to mitochondrial morphology alteration and dysfunction. Enhanced understanding of the molecular mechanisms in depth may shed light on the therapy of the disease. In this study, we show that mitochondrial fission factor (MFF) is up-regulated upon hypertrophic agonist noradrenaline (NA) treatment. Knockdown of MFF attenuated NA induced mitochondrial fission and cardiac hypertrophy. Mitochondrial fission factor is a direct target of miR-376b-3p, which attenuated expression enhanced MFF expression through binding to its 3'UTR. Expression of miR-376b-3p weakened the fragmentation of mitochondria as well as decreased hypertrophic response through regulating MFF in NA treated neonatal rat ventricular cells (NRVCs). This study suggested that miR-376b-3p is a novel modulator affecting mitochondrial morphology through targeting MFF.

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Section: Discussionsupporting

confidence: 55%

miR‐376b‐3p attenuates mitochondrial fission and cardiac hypertrophy by targeting mitochondrial fission factor

Sun

Yang

et al. 2018

Clin Exp Pharma Physio

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“…Whether the localisation of PDE2A at mitochondrial membranes is related to the anti-hypertrophic effect of PDE2A inhibition in cardiac myocytes remains to be established. However, it is interesting to note that knock down of the mitochondrial fusion protein mitofusin 2, which results in fragmented mitochondria, also leads to cardiac myocyte hypertrophy, suggesting a possible direct link between mitochondria fragmentation and cardiac myocytes hypertrophic growth (Pennanen et al, 2014; Guan et al, 2016). …”

Section: Discussionmentioning

confidence: 99%

PDE2A2 regulates mitochondria morphology and apoptotic cell death via local modulation of cAMP/PKA signalling

Monterisi

Lobo

Livie

et al. 2017

eLife

109

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cAMP/PKA signalling is compartmentalised with tight spatial and temporal control of signal propagation underpinning specificity of response. The cAMP-degrading enzymes, phosphodiesterases (PDEs), localise to specific subcellular domains within which they control local cAMP levels and are key regulators of signal compartmentalisation. Several components of the cAMP/PKA cascade are located to different mitochondrial sub-compartments, suggesting the presence of multiple cAMP/PKA signalling domains within the organelle. The function and regulation of these domains remain largely unknown. Here, we describe a novel cAMP/PKA signalling domain localised at mitochondrial membranes and regulated by PDE2A2. Using pharmacological and genetic approaches combined with real-time FRET imaging and high resolution microscopy, we demonstrate that in rat cardiac myocytes and other cell types mitochondrial PDE2A2 regulates local cAMP levels and PKA-dependent phosphorylation of Drp1. We further demonstrate that inhibition of PDE2A, by enhancing the hormone-dependent cAMP response locally, affects mitochondria dynamics and protects from apoptotic cell death.DOI: http://dx.doi.org/10.7554/eLife.21374.001

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“…Cell surface area was measured as previously described in detail. 11 Briefly, cardiomyocytes were fixed with 4% paraformaldehyde for 20 minutes, penetrated by 0.4% Triton X-100 for 1 hour and then blocked by goat serum at 37°C for 1 hour. The cells were first incubated with anti-sarcomeric alpha actinin antibody (1:250; Abcam) at 4°C overnight and subsequently with a DyLight 594 goat anti-mouse antibody at room temperature for 1 hour.…”

Section: Measurement Of Cell Surface Areamentioning

confidence: 99%

“…We have previously characterized the lncRNA expression signature using microarray analysis in conjunction with real‐time RT‐PCR methods in a mouse model of CH induced by pressure overload after transverse aortic constriction (TAC) and identified a particular lncRNA AK134605 with its expression robustly down‐regulated in CH . We have also demonstrated that the expression of miR‐20b was significantly up‐regulated in CH . The objectives of the present study were to examine whether AK134605 plays a role in CH and, if yes, then to decipher the underlying mechanisms for the action of this lncRNA in CH.…”

Section: Introductionmentioning

confidence: 99%

Long non‐coding RNA cardiac hypertrophy‐associated regulator governs cardiac hypertrophy via regulating miR‐20b and the downstream PTEN/AKT pathway

Zhang

Jiang

Guo

et al. 2019

J Cellular Molecular Medi

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Pathological cardiac hypertrophy (CH) is a key factor leading to heart failure and ultimately sudden death. Long non‐coding RNAs (lncRNAs) are emerging as a new player in gene regulation relevant to a wide spectrum of human disease including cardiac disorders. Here, we characterize the role of a specific lncRNA named cardiac hypertrophy‐associated regulator (CHAR) in CH and delineate the underlying signalling pathway. CHAR was found markedly down‐regulated in both in vivo mouse model of cardiac hypertrophy induced by pressure overload and in vitro cellular model of cardiomyocyte hypertrophy induced by angiotensin II (AngII) insult. CHAR down‐regulation alone was sufficient to induce hypertrophic phenotypes in healthy mice and neonatal rat ventricular cells (NRVCs). Overexpression of CHAR reduced the hypertrophic responses. CHAR was found to act as a competitive endogenous RNA (ceRNA) to down‐regulate miR‐20b that we established as a pro‐hypertrophic miRNA. We experimentally established phosphatase and tensin homolog (PTEN), an anti‐hypertrophic signalling molecule, as a target gene for miR‐20b. We found that miR‐20b induced CH by directly repressing PTEN expression and indirectly increasing AKT activity. Moreover, CHAR overexpression mitigated the repression of PTEN and activation of AKT by miR‐20b, and as such, it abrogated the deleterious effects of miR‐20b on CH. Collectively, this study characterized a new lncRNA CHAR and unravelled a new pro‐hypertrophic signalling pathway: lncRNA‐CHAR/miR‐20b/PTEN/AKT. The findings therefore should improve our understanding of the cellular functionality and pathophysiological role of lncRNAs in the heart.

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miR-106a promotes cardiac hypertrophy by targeting mitofusin 2

Cited by 64 publications

References 51 publications

miR‐376b‐3p attenuates mitochondrial fission and cardiac hypertrophy by targeting mitochondrial fission factor

miR‐376b‐3p attenuates mitochondrial fission and cardiac hypertrophy by targeting mitochondrial fission factor

PDE2A2 regulates mitochondria morphology and apoptotic cell death via local modulation of cAMP/PKA signalling

Long non‐coding RNA cardiac hypertrophy‐associated regulator governs cardiac hypertrophy via regulating miR‐20b and the downstream PTEN/AKT pathway

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