Cardiac hypertrophy and dysfunction induced by overexpression of miR-214 in vivo

Yang, Tao; Gu, Haihua; Chen, Xiaofan; Fu, Shaozhi; Xu, Hongfei; Feng, Qiang; Ni, Yiming

doi:10.1016/j.jss.2014.06.044

Cited by 27 publications

(27 citation statements)

References 36 publications

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“…Expression of miR-214 is deregulated in many tumours including pancreatic cancer, melanoma, and hepatocellular carcinoma (Zhang et al , 2010; Penna et al , 2013; Zhang et al , 2015), whereas upregulated in breast cancer by targeting p53 (Wang et al , 2015). The pleiotropic and tumour-specific of miR-214 contributes to various cancer formation and progression via its several target genes including p53 , Bcl-2/Bax , TFAM , EZH2 (Wen et al , 2014; Yang et al , 2014; Tian et al , 2015). Recently, Chen et al (2014) reported that miR-214 negatively regulated liver metastasis in CRC.…”

Section: Discussionmentioning

confidence: 99%

The FOXD3/miR-214/MED19 axis suppresses tumour growth and metastasis in human colorectal cancer

Zhou

et al. 2016

Br J Cancer

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Background: MiR-214 is aberrantly regulated in several tumours, but its underlying mechanisms in colorectal cancer (CRC) metastasis remain largely unknown. This study aimed to demonstrate the function and potential mechanism of miR-214 in regulating invasion and metastasis of CRC. Methods:The transcription factor and targets of miR-214 were predicted by bioinformatics and validated using ChIP and dual-luciferase reporter assay. DNA methylation status was explored using bisulphite sequencing PCR. The in vitro and in vivo function of miR-214 in CRC was evaluated using MTT, plate colony formation, Matrigel invasion and animal models. Real-time PCR or western blotting was performed to detect FOXD3, miR-214 and MED19 expressions in CRC cells and clinical specimens.Results: MiR-214 was downregulated in CRC and was significantly correlated with lymphatic metastasis. Downregulation of miR-214 might due to promoter hypermethylation in CRC. FOXD3 was validated as a transcription factor of miR-214 by ChIP assay. Dual-luciferase assay identified MED19 as a target of miR-214 in CRC. In vitro and in vivo experiments showed that miR-214 mediated the inhibiting effect of FOXD3 on proliferation, invasion and metastasis by targeting MED19. Spearman's correlation analysis showed a positive correlation between FOXD3 and miR-214, and negative correlations between FOXD3 and MED19, miR-214 and MED19 in CRC cells and clinical specimens.Conclusions: FOXD3/miR-214/MED19 axis is important for the regulation of growth, invasion and metastasis of CRC. Targeting the miR-214-mediated axis might be helpful for the treatment of CRC.

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Section: Discussionmentioning

confidence: 99%

The FOXD3/miR-214/MED19 axis suppresses tumour growth and metastasis in human colorectal cancer

Zhou

et al. 2016

Br J Cancer

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“…However, one study showed that downregulation of miR-214 by antagonists attenuated cardiac fibroblast proliferation and collagen synthesis via inhibition of Mfn2 and activation of ERK1/2 MAPK signaling [18]. Similarly, knockdown of miR-214 in vivo using a specific antagomir (miR-214 inhibitor) prevented cardiac remodeling and dysfunction in a mouse heart failure model of pressure overload [26]. Collectedly, the role and potential target gene of miR-214 in cardiac fibrosis have not been well-illustrated.…”

Section: Discussionmentioning

confidence: 99%

Targeting EZH1 and EZH2 contributes to the suppression of fibrosis-associated genes by miR-214-3p in cardiac myofibroblasts

et al. 2016

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The role of microRNA-214-3p (miR-214-3p) in cardiac fibrosis was not well illustrated. The present study aimed to investigate the expression and potential target of miR-214-3p in angiotensin II (Ang-II)-induced cardiac fibrosis. MiR-214-3p was markedly decreased in the fibrotic myocardium of a mouse Ang-II infusion model, but was upregulated in Ang-II-treated mouse myofibroblasts. Cardiac fibrosis was shown attenuated in Ang-II-infused mice received tail vein injection of miR-214-3p agomir. Consistently, miR-214-3p inhibited the expression of Col1a1 and Col3a1 in mouse myofibroblasts in vitro. MiR-214-3p could bind the 3′-UTRs of enhancer of zeste homolog 1 (EZH1) and −2, and suppressed EZH1 and −2 expressions at the transcriptional level. Functionally, miR-214-3p mimic, in parallel to EZH1 siRNA and EZH2 siRNA, could enhance peroxisome proliferator-activated receptor-γ (PPAR-γ) expression and inhibited the expression of Col1a1 and Col3a1 in myofibroblasts. In addition, enforced expression of EZH1 and −2, and knockdown of PPAR-γ resulted in the increase of Col1a1 and Col3a1 in myofibroblasts. Moreover, the NF-κB signal pathway was verified to mediate Ang-II-induced miR-214-3p expression in myofibroblasts. Taken together, our results revealed that EZH1 and −2 were novel targets of miR-214-3p, and miR-214-3p might be one potential miRNA for the prevention of cardiac fibrosis.

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“…Enforced expression of miR-214 could increase cell size of rat cardiomyocytes and the expression of ANP, Acta1 and β-MHC7. Moreover, obvious cardiac hypertrophy phenotype was obtained in the transgenic mice with cardiomyocyte-specific overexpression of miR-21421. The enhancer of zeste homolog 2 (EZH2) was reported to be a direct target of miR-214 during cardiac hypertrophy in vitro and in vivo 721.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, obvious cardiac hypertrophy phenotype was obtained in the transgenic mice with cardiomyocyte-specific overexpression of miR-21421. The enhancer of zeste homolog 2 (EZH2) was reported to be a direct target of miR-214 during cardiac hypertrophy in vitro and in vivo 721. However, a recent study revealed that interaction of EZH2 and primary microRNA-208b (pri-miR-208b) regulates hypertrophic gene expression, and attenuation of EZH2 can restore antisense β-MHC and α-MHC gene expression, and inhibit cardiac hypertrophy22.…”

Section: Discussionmentioning

confidence: 99%

Myocyte-specific enhancer factor 2C: a novel target gene of miR-214-3p in suppressing angiotensin II-induced cardiomyocyte hypertrophy

Tang

Liu

Zhu

et al. 2016

Sci Rep

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The role of microRNA-214-3p (miR-214-3p) in cardiac hypertrophy was not well illustrated. The present study aimed to investigate the expression and potential target of miR-214-3p in angiotensin II (Ang-II)-induced mouse cardiac hypertrophy. In mice with either Ang-II infusion or transverse aortic constriction (TAC) model, miR-214-3p expression was markedly decreased in the hypertrophic myocardium. Down-regulation of miR-214-3p was observed in the myocardium of patients with cardiac hypertrophy. Expression of miR-214-3p was upregulated in Ang-II-induced hypertrophic neonatal mouse ventricular cardiomyocytes. Cardiac hypertrophy was attenuated in Ang-II-infused mice by tail vein injection of miR-214-3p. Moreover, miR-214-3p inhibited the expression of atrial natriuretic peptide (ANP) and β-myosin heavy chain (MHC) in Ang-II-treated mouse cardiomyocytes in vitro. Myocyte-specific enhancer factor 2C (MEF2C), which was increased in Ang-II-induced hypertrophic mouse myocardium and cardiomyocytes, was identified as a target gene of miR-214-3p. Functionally, miR-214-3p mimic, consistent with MEF2C siRNA, inhibited cell size increase and protein expression of ANP and β-MHC in Ang-II-treated mouse cardiomyocytes. The NF-κB signal pathway was verified to mediate Ang-II-induced miR-214-3p expression in cardiomyocytes. Taken together, our results revealed that MEF2C is a novel target of miR-214-3p, and attenuation of miR-214-3p expression may contribute to MEF2Cexpressionin cardiac hypertrophy.

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Cardiac hypertrophy and dysfunction induced by overexpression of miR-214 in vivo

Cited by 27 publications

References 36 publications

The FOXD3/miR-214/MED19 axis suppresses tumour growth and metastasis in human colorectal cancer

The FOXD3/miR-214/MED19 axis suppresses tumour growth and metastasis in human colorectal cancer

Targeting EZH1 and EZH2 contributes to the suppression of fibrosis-associated genes by miR-214-3p in cardiac myofibroblasts

Myocyte-specific enhancer factor 2C: a novel target gene of miR-214-3p in suppressing angiotensin II-induced cardiomyocyte hypertrophy

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