MicroRNA-101 Inhibits Rat Cardiac Hypertrophy by Targeting Rab1a

Wei, Longxiao; Yuan, Menghui; Zhou, Ru; Bai, Qianrong; Zhang, Wei; Zhang, Ming; Huang, Yong; Shi, Le

doi:10.1097/fjc.0000000000000203

Cited by 29 publications

(16 citation statements)

References 26 publications

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“…In cardiac myocytes, increased Rab1A level facilitates cardiomyocyte hypertrophic growth in response to stimulation by angiostensin II (Ang II) and phenylephrine (PE) 17 . More recently, it was shown that up-regulation of miR-101 in a rat model of cardiac hypertrophic model protects against Rab1A-induced myocardial hypertrophy and heart failure, suggesting that miR-101 is potentially useful for therapeutic intervention of cardiomyopathy 62 . Thus far, the precise mechanism of Rab1A in cardiac pathogenesis remains unclear.…”

Section: Cardiomyopathymentioning

confidence: 99%

Rab1 in cell signaling, cancer and other diseases

Yang

Zhang

et al. 2016

Oncogene

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The ER and Golgi membrane system plays major roles in cell signaling and regulation of the biosynthesis/transport of proteins and lipids in response to environmental cues such as amino acid and cholesterol levels. Rab1 is the founding member of the Rab small GTPase family, which is known to mediate dynamic membrane trafficking between ER and Golgi. Growing evidence indicate that Rab1 proteins have important functions beyond their classical vesicular transport functions, including nutrient sensing and signaling, cell migration, and presentation of cell surface receptors. Moreover, deregulation of RAB1 expression has been linked to a myriad of human diseases such as cancer, cardiomyopathy and Parkinson’s disease. Further investigating these new physiological and pathological functions of Rab1 should provide new opportunities for better understanding of the disease processes and may lead to more effective therapeutic interventions.

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Section: Cardiomyopathymentioning

confidence: 99%

Rab1 in cell signaling, cancer and other diseases

Yang

Zhang

et al. 2016

Oncogene

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“…Several miRNAs exert anti-hypertrophic roles, such as miR-133, for example, which targets the hypertrophic regulatory factors, RhoA and Cdc42, to inhibit cardiac hypertrophy (13), and miR-1, whose attenuation evokes hypertrophy (14). Furthermore, miR-101 suppresses hypertrophy in the rat heart via inhibition of its target gene, Rab1a (15). In general, miRNA-mediated gene expression and the regulation of further downstream signaling events exert an appreciable influence on the progression of cardiac hypertrophy, the details of which have yet to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-26a protects against cardiac hypertrophy via inhibiting GATA4 in rat model and cultured cardiomyocytes

Liu

Wang

Xiao

2016

Molecular Medicine Reports

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Pathological cardiac hypertrophy is characterized by deleterious changes developed in cardiovascular diseases, whereas microRNAs (miRNAs) are involved in the mediation of cardiac hypertrophy. To investigate the role of microRNA-26a (miR-26a) in regulating cardiac hypertrophy and its functioning mechanisms, overexpression and suppression of miR‑26a via its mimic and inhibitor in a transverse abdominal aortic constriction (TAAC)-induced rat model and in angiotensin II (Ang II)-induced cardiomyocytes (CMs) was performed. In the rat model, the heart weight (HW) compared with the body weight (BW), the CM area, and expression of the hypertrophy‑associated factors, atrial natriuretic factor (ANF) and β‑myosin heavy chain (β‑MHC), were assessed. In CMs, the protein synthesis rate was determined using a leucine incorporation assay. Mutation of the GATA‑binding protein 4 (GATA4) 3'‑untranslated region (UTR) and overexpression of GATA4 were performed to confirm whether GATA4 is the target of miR‑26a. The results indicated that miR-26a was significantly downregulated in the heart tissue of the rat model, as well as in Ang II‑induced CMs (P<0.05). The TAAC-induced rat model exhibited a higher HW/BW ratio, a larger CM area, and higher expression levels of ANF and β‑MHC. CMs, upon Ang II treatment, also demonstrated a larger CM area, higher levels of ANF and β‑MHC, as well as accelerated protein synthesis. miR‑26a was not able to regulate GATA4 with mutations in the 3'‑UTR, indicating that GATA4 was the direct target of miR‑26a. Overexpression of GATA4 abrogated the inhibitory functions of miR‑26a in cardiac hypertrophy. Taken together, the present study suggested an anti‑hypertrophic role of miR‑26a in cardiac hypertrophy, possibly via inhibition of GATA4. These findings may be useful in terms of facilitating cardiac treatment, with potential therapeutic targets and strategies.

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“…MiRNA-101 overexpression inhibits fibrosis and adverse cardiac remodelling through inhibition of c-FOS, a transcriptional modulator of TGFb (63). In a rat model of hypertrophy, miRNA-101 overexpression inhibited cardiomyocytes hypertrophy through the downregulation of its target small GTPase Rab1a (64). Finally, miRNA-101 is downregulated upon VEGF treatment, resulting in increased expression of the histone methyltransferase EZH2 in endothelial cells and promotion of angiogenesis (65).…”

Section: Mirna-101mentioning

confidence: 99%

Molecular therapies delaying cardiovascular aging: disease- or health-oriented approaches

et al. 2020

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Regenerative medicine is a new therapeutic modality that aims to mend tissue damage by encouraging the reconstitution of physiological integrity. It represents an advancement over conventional therapies that allow reducing the damage but result in disease chronicization. Age-related decline in spontaneous capacity of repair, especially in organs like the heart that have very limited proliferative capacity, contributes in reducing the benefit of conventional therapy. ncRNAs are emerging as key epigenetic regulators of cardiovascular regeneration. Inhibition or replacement of miRNAs may offer reparative solutions to cardiovascular disease. The first part of this review article is devoted to illustrating novel therapies emerging from research on miRNAs. In the second part, we develop new therapeutic concepts emerging from genetics of longevity. Prolonged survival, as in supercentenarians, denotes an exceptional capacity to repair and cope with risk factors and diseases. These characteristics are shared with offspring, suggesting that the regenerative phenotype is heritable. New evidence indicates that genetic traits responsible for prolongation of health span in humans can be passed to and benefit the outcomes of animal models of cardiovascular disease. Genetic studies have also focused on determinants of accelerated senescence and related druggable targets. Evolutionary genetics assessing the genetic basis of adaptation and comparing successful and unsuccessful genetic changes in response to selection within populations represent a powerful basis to develop novel therapies aiming to prolong cardiovascular and whole organism health.

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MicroRNA-101 Inhibits Rat Cardiac Hypertrophy by Targeting Rab1a

Cited by 29 publications

References 26 publications

Rab1 in cell signaling, cancer and other diseases

Rab1 in cell signaling, cancer and other diseases

MicroRNA-26a protects against cardiac hypertrophy via inhibiting GATA4 in rat model and cultured cardiomyocytes

Molecular therapies delaying cardiovascular aging: disease- or health-oriented approaches

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