MIAT Is a Pro-fibrotic Long Non-coding RNA Governing Cardiac Fibrosis in Post-infarct Myocardium

Qu, Xueping; Du, Yue; You, Sylvaine; Gao, Ming; Sun, Fan; Luo, Shenjian; Yang, Ti; Zhan, Linfeng; Yuan, Yin; Chu, Wenfeng; Pan, Zhenwei; Wang, Zhiguo; Yang, Baofeng; Lu, Yanjie

doi:10.1038/srep42657

Cited by 177 publications

(140 citation statements)

References 30 publications

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“…The upregulation of MIAT in MI is accompanied by the imbalance of some fibrosis-related regulatory factors, such as mir-24 (down-regulation), furin, and TGF-b1 (upregulation). However, siRNA-mediated endogenous MIAT knockout lowered myocardial fibrosis and reestablished the dysregulation of fibrosis-related regulatory factors [31]. Similarly, Wisrier expression is associated with fibrosis in cardiac mouse model and human tissue of a human patient with aortic stenosis.…”

Section: Discussionmentioning

confidence: 98%

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Long noncoding RNA Crnde attenuates cardiac fibrosis via Smad3‐Crnde negative feedback in diabetic cardiomyopathy

Zheng¹,

Zhang²,

Hu³

et al. 2019

The FEBS Journal

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Diabetic cardiomyopathy (DCM)—ventricular dysfunction in the absence of underlying heart disease—is a common complication of diabetes and a leading cause of mortality associated with the disease. In DCM, cardiac fibrosis is the main cause of heart failure. Although it is well‐established that the transforming growth factor‐beta signaling pathway plays a part in inducing cardiac fibrosis in DCM, details of the molecular mechanism involved remain elusive. Therefore, it is crucial to study the gene reg;ulation of key signaling effectors in DCM‐associated cardiac fibrosis. A recently emerged hotspot in the field of gene regulation is the role of long noncoding RNAs (lncRNAs). Recent evidence indicates that lncRNAs play a critical role in cardiac fibrosis; however, in DCM, the function of these regulatory RNAs have not been studied in depth. In this study, we identified a conserved cardiac‐specific lncRNA named colorectal neoplasia differentially expressed (Crnde). By analyzing 376 human heart tissues, it was found that Crnde expression is negatively correlated with that of cardiac fibrosis marker genes. Moreover, Crnde expression was shown to be enriched in cardiac fibroblasts (CFs). Overexpression of Crnde attenuated cardiac fibrosis and enhanced cardiac function in mice with DCM. Further, in vitro experiments showed that Crnde negatively regulates the myofibroblast differentiation of CFs. The expression of Crnde was activated by SMAD family member 3 (Smad3), shedding light on the underlying molecular mechanism. Interestingly, Crnde also inhibited the transcriptional activation of Smad3 on target genes, thereby inhibiting the expression of myofibroblastic marker genes in CFs. Overall, our data provide valuable insights into the development of potential anti‐cardiac fibrosis strategies centered on lncRNAs, for the treatment of DCM.

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Section: Discussionmentioning

confidence: 98%

“…However, siRNA‐mediated endogenous MIAT knockout lowered myocardial fibrosis and reestablished the dysregulation of fibrosis‐related regulatory factors . Similarly, Wisrier expression is associated with fibrosis in cardiac mouse model and human tissue of a human patient with aortic stenosis.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA Crnde attenuates cardiac fibrosis via Smad3‐Crnde negative feedback in diabetic cardiomyopathy

Zheng¹,

Zhang²,

Hu³

et al. 2019

The FEBS Journal

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show abstract

“…3 LncRNAs participate in a number of biological processes and pathophysiological events including cancers and cardiovascular disease. 4 LncRNAs have been demonstrated to regulate cardiac hypertrophy, mitochondrial function, cardiac fibrosis and apoptosis of cardiomyocyte. 5 For example, the expression of Meg3 (maternally expressed gene 3) was up-regulated in mouse injured heart after MI and involved in the regulation of apoptosis via binding to RNAbinding protein FUS (fused in sarcoma).…”

mentioning

confidence: 99%

LncRNA ACART protects cardiomyocytes from apoptosis by activating PPAR‐γ/Bcl‐2 pathway

Zhu

Zhuang

et al. 2019

J Cellular Molecular Medi

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Cardiomyocyte apoptosis is an important process occurred during cardiac ischaemia‐reperfusion injury. Long non‐coding RNAs (lncRNA) participate in the regulation of various cardiac diseases including ischaemic reperfusion (I/R) injury. In this study, we explored the potential role of lncRNA ACART (anti‐cardiomyocyte apoptosis‐related transcript) in cardiomyocyte injury and the underlying mechanism for the first time. We found that ACART was significantly down‐regulated in cardiac tissue of mice subjected to I/R injury or cultured cardiomyocytes treated with hydrogen peroxide (H2O2). Knockdown of ACART led to significant cardiomyocyte injury as indicated by reduced cell viability and increased apoptosis. In contrast, overexpression of ACART enhanced cell viability and reduced apoptosis of cardiomyocytes treated with H2O2. Meanwhile, ACART increased the expression of the B cell lymphoma 2 (Bcl‐2) and suppressed the expression of Bcl‐2‐associated X (Bax) and cytochrome‐C (Cyt‐C). In addition, PPAR‐γ was up‐regulated by ACART and inhibition of PPAR‐γ abolished the regulatory effects of ACART on cell apoptosis and the expression of Bcl‐2, Bax and Cyt‐C under H2O2 treatment. However, the activation of PPAR‐γ reversed the effects of ACART inhibition. The results demonstrate that ACART protects cardiomyocyte injury through modulating the expression of Bcl‐2, Bax and Cyt‐C, which is mediated by PPAR‐γ activation. These findings provide a new understanding of the role of lncRNA ACART in regulation of cardiac I/R injury.

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“…It has been reported that MIAT is associated with neurovascular dysfunction (Bountali et al, 2019;Qu et al, 2017;Yan et al, 2015). At the same time, MIAT is found to be upregulated in the peripheral blood of ischemic stroke (M. Zhu et al, 2018).…”

Section: Dual Luciferase Reporter Gene Assaymentioning

confidence: 99%

Long noncoding MIAT acting as a ceRNA to sponge microRNA‐204‐5p to participate in cerebral microvascular endothelial cell injury after cerebral ischemia through regulating HMGB1

Deng

Fan

Shen

et al. 2019

Journal Cellular Physiology

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This study is applied to the investigation of the long noncoding RNA myocardial infarction associated transcript's (MIAT's) role in regulating the expression of highmobility group box 1 (HMGB1) in cerebral microvascular endothelial cell (CMEC) injury after cerebral ischemia by serving as a competitive endogenous RNA (ceRNA) to sponge microRNA-204-5p (miR-204-5p). The cerebral ischemia model of middle cerebral artery occlusion (MCAO) in rats was established by the suture method, in which rats were injected with empty plasmids and MIAT siRNA plasmids. The cerebral ischemia injury model in vitro was established through oxygen glucose deprivation (OGD) in primary cultured CMECs in rats. The cells were transfected with empty plasmids and MIAT siRNA plasmids. The MIAT/miR-204-5p/HMGB1 axis' function in damage and angiogenesis of CMECs were explored. The binding site between MIAT and miR-204-5p along with that between miR-204-5p and HMGB1 was determined. MIAT was overexpressed in MCAO rats' brain tissue and inhibited MIAT attenuated the injury of brain tissue in MCAO rats. Inhibition of MIAT promoted angiogenesis, promoted miR-204-5p expression and inhibited HMGB1 expression in brain tissue of MCAO rats. Inhibition of MIAT reduced CMEC damage, induced angiogenesis of CMECs, increased the number of surviving neurons, promoted miR-204-5p expression and inhibited HMGB1 expression in CMECs treated with OGD. MIAT promoted HMGB1 expression by competitive binding to miR-204-5p to regulate the injury of CMECs after cerebral ischemia. Our study showed that MIAT promoted HMGB1 expression by competitively binding to miR-204-5p to regulate the injury of CMECs after cerebral ischemia. K E Y W O R D S cerebral ischemia, cerebral microvascular endothelial cells injury, HMGB1, long noncoding MIAT, microRNA-204-5p

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MIAT Is a Pro-fibrotic Long Non-coding RNA Governing Cardiac Fibrosis in Post-infarct Myocardium

Cited by 177 publications

References 30 publications

Long noncoding RNA Crnde attenuates cardiac fibrosis via Smad3‐Crnde negative feedback in diabetic cardiomyopathy

Long noncoding RNA Crnde attenuates cardiac fibrosis via Smad3‐Crnde negative feedback in diabetic cardiomyopathy

LncRNA ACART protects cardiomyocytes from apoptosis by activating PPAR‐γ/Bcl‐2 pathway

Long noncoding MIAT acting as a ceRNA to sponge microRNA‐204‐5p to participate in cerebral microvascular endothelial cell injury after cerebral ischemia through regulating HMGB1

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