The Long Noncoding RNA CAREL Controls Cardiac Regeneration

Cai, Benzhi; Ma, Wanbiao; Ding, Fengzhi; Zhang, Lai; Huang, Qi; Wang, Xiuxiu; Hua, Bingjie; Xu, Juan; Li, Jiamin; Bi, Chongwei; Guo, Shuyuan; Yang, Fan; Han, Zhenbo; Li, Yuan; Yan, Gege; Yu, Ying; Bao, Zhengyi; Yu, Meixi; Li, Faqian; Tian, Ye; Pan, Zhenwei; Yang, Baofeng

doi:10.1016/j.jacc.2018.04.085

Cited by 123 publications

(91 citation statements)

References 25 publications

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“…For example, Micheletti et al showed that lncRNA Wisper could reduce the pathological development of cardiac fibrosis in response to MI and prevent adverse remodeling in the damaged heart [10]. Cai et al found that lncRNA CAREL regulated cardiomyocyte proliferation and heart regeneration in postnatal and adult heart after injury by miR-296/Trp53inp1/ Itm2a axis [11]. Recently, Hu et al reported that lncRNA MALAT1 inhibition attenuated acute MI through miR-320-Pten axis [12].…”

Section: Introductionmentioning

confidence: 99%

LINC00528 regulates myocardial infarction by targeting the miR-143-3p/COX-2 axis

2019

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This study is aimed to explore the roles of LINC00528 in myocardial infarction (MI) progression. Quantitative real-time PCR showed that the expression of LINC00528 and COX-2 was upregulated while miR-143-3p expression was down-regulated in post-MI cells. In function assays, LINC00528 suppression promoted post-MI cells proliferation and reduced cell apoptosis in vitro. In mechanism, LINC00528 interacted with miR-143-3p in post-MI cells. COX-2 served as a target of miR-143-3p in post-MI cells. Besides, LINC00528 inhibition on COX-2 expression and post-MI cells progression could be partially abolished by miR-143-3p inhibitors. Therefore, our findings suggested that LINC00528 exerted its regulatory roles in MI via the miR-143-3p/COX-2 axis, which provided a potential therapeutic target for MI patients treatment. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

LINC00528 regulates myocardial infarction by targeting the miR-143-3p/COX-2 axis

2019

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“…Several lncRNAs have been reported to have roles in regulating heart development and function. For example, depletion of Chast/Wisper and overexpression of Mhrt, Tincr or Carel protected the heart from hypertrophy in response to pressure overload following transverse aortic constriction surgery (Cai et al, 2018;Han et al, 2014b;Micheletti et al, 2017;Shao et al, 2017;Viereck et al, 2016). Inhibition of Fendrr led to embryonic lethality around E13.5 with cardiac hypoplasia (Grote et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

The lncRNA Hand2os1/Uph locus orchestrates heart development through regulation of precise expression of Hand2

et al. 2019

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Exploration and dissection of potential actions and effects of long noncoding RNA (lncRNA) in animals remain challenging. Here, using multiple knockout mouse models and single cell RNA sequencing, we demonstrate that the divergent lncRNA Hand2os1/Uph has a key complex modulatory effect on the expression of its neighboring gene HAND2 and subsequently on heart development and function. Short deletion of the Hand2os1 promoter in mouse diminishes Hand2os1 transcription to ∼8-32%, but fails to affect HAND2 expression and yields no discernable heart phenotypes. Interestingly, full-length deletion of Hand2os1 in mouse causes moderate yet prevalent upregulation of HAND2 in hundreds of cardiac cells, leading to profound biological consequences, including dysregulated cardiac gene programs, congenital heart defects and perinatal lethality. We propose that the Hand2os1 locus dampens HAND2 expression to restrain cardiomyocyte proliferation, thereby orchestrating a balanced development of cardiac cell lineages. This study highlights the regulatory complexity of the lncRNA Hand2os1 on HAND2 expression, emphasizing the need for complementary genetic and single cell approaches to delineate the function and primary molecular effects of an lncRNA in animals.

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“…LncRNAs are distributed in both the nucleus and cytoplasm and regulate intracellular signaling pathways via different mechanisms, including chromatin modification, gene transcription regulation, and competing endogenous RNAs (ceRNAs) [48]. Among these, ceRNAs have a potentially important role in cardiac-related diseases [49,50]. Recent studies revealed that cardiac hypertrophy-related factor regulated cardiac hypertrophy by targeting miR-489.…”

Section: Discussionmentioning

confidence: 99%

LncRNA-NEAT1 from the competing endogenous RNA network promotes cardioprotective efficacy of mesenchymal stem cell-derived exosomes induced by macrophage migration inhibitory factor via the miR-142-3p/FOXO1 signaling pathway

2020

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Aims: Extracellular vesicles, especially exosomes, have emerged as key mediators of intercellular communication with the potential to improve cardiac function as part of cell-based therapies. We previously demonstrated that the cardioprotective factor, macrophage migration inhibitory factor (MIF), had an optimizing effect on mesenchymal stem cells (MSCs). The aim of this study was to determine the protective function of exosomes derived from MIFpretreated MSCs in cardiomyocytes and to explore the underlying mechanisms. Methods and results: Exosomes were isolated from control MSCs (exosome) and MIF-pretreated MSCs (exosome MIF), and delivered to cardiomyocytes subjected to H 2 O 2 in vitro. Regulatory long non-coding RNAs (lncRNAs) activated by MIF pretreatment were explored using genomics approaches. Exosome MIF protected cardiomyocytes from H 2 O 2-induced apoptosis. Mechanistically, we identified lncRNA-NEAT1 as a mediator of exosome MIF by regulating the expression of miR-142-3p and activating Forkhead class O1 (FOXO1). The cardioprotective effects of exosome MIF were consistently abrogated by depletion of lncRNA-NEAT1, by overexpression of miR-142-3p, or by FOXO1 silencing. Furthermore, exosome MIF inhibited H 2 O 2-induced apoptosis through modulating oxidative stress. Conclusions: Exosomes obtained from MIF-pretreated MSCs have a protective effect on cardiomyocytes. The lncRNA-NEAT1 functions as an anti-apoptotic molecule via competitive endogenous RNA activity towards miR-142-3p. LncRNA-NEAT1/miR-142-3p/FOXO1 at least partially mediates the cardioprotective roles of exosome MIF in protecting cardiomyocytes from apoptosis.

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The Long Noncoding RNA CAREL Controls Cardiac Regeneration

Abstract: LncRNA CAREL regulates cardiomyocyte proliferation and heart regeneration in postnatal and adult heart after injury by acting as a competing endogenous ribonucleic acid on miR-296 that targets Trp53inp1 and Itm2a.

Cited by 123 publications

References 25 publications

LINC00528 regulates myocardial infarction by targeting the miR-143-3p/COX-2 axis

LINC00528 regulates myocardial infarction by targeting the miR-143-3p/COX-2 axis

The lncRNA Hand2os1/Uph locus orchestrates heart development through regulation of precise expression of Hand2

LncRNA-NEAT1 from the competing endogenous RNA network promotes cardioprotective efficacy of mesenchymal stem cell-derived exosomes induced by macrophage migration inhibitory factor via the miR-142-3p/FOXO1 signaling pathway

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