Small molecules, big effects: the role of microRNAs in regulation of cardiomyocyte death

Skommer, Joanna; Rana, Indrajeetsinh; Marques, Francine Z.; Zhu, Wenliang; Du, Zhenhong; Charchar, Fadi J.

doi:10.1038/cddis.2014.287

Cited by 50 publications

(33 citation statements)

References 194 publications

(166 reference statements)

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“…Endothelial dysfunction is regarded as one of the significant reason for cardiovascular disease [24]. Increasing evidence has elucidated that mRNAs play a key role in regulating myocardial apoptosis [25, 26]. In our study, we verified the roles of miR-499 and PDCD4 in endothelial cells during CAD.…”

Section: Discussionsupporting

confidence: 65%

Effects of MicroRNA-499 On the Inflammatory Damage of Endothelial Cells During Coronary Artery Disease Via the Targeting of PDCD4 Through the NF-Κβ/TNF-α Signaling Pathway

Zhang¹,

He²,

Shi³

2017

Cell Physiol Biochem

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Background/Aims: This study aimed to analyze the impact of microRNA-499 (miR-499) on the inflammatory damage of endothelial cells during coronary artery disease (CAD) via the targeting of PDCD4 through the NF-kB/ TNF-α signaling pathway. Methods: A total of 216 CAD patients (CAD group) and 90 healthy people (normal group) were enrolled in our study. Endothelial cells were collected and assigned into normal, OX-LDL, negative control (NC), miR-499 inhibitor, miR-499 mimic, PDCD4 siRNA, and miR-499 inhibitor + PDCD4 siRNA groups. The qRT-PCR and western blotting were performed to detect the mRNA and protein expression levels of PDCD4 and miR-499. The MTT assay was performed to determine cell viability, ELISA was performed to determine the expression levels of inflammatory factors, and flow cytometry assay to evaluate cell apoptosis. Results: Increased miR-499 expression and decreased PDCD4 expression in the plasma were observed in the CAD group compared with the normal group, demonstrating a negative correlation between miR-499 and PDCD4. Compared to the normal and miR-499 inhibitor groups, the survival rate of cells and PDCD4 expression were decreased; and the expressions of miR-499, IL-6, IL-8, IL-1β, TNF-α, NF-kB, VCAM-1, ICAM-1 and MCP-1 and the apoptosis rate were all elevated in the OX-LDL, NC, miR-499 mimic, PDCD4 siRNA and miR-499 inhibitor + PDCD4 siRNA groups. Compared to the OX-LDL, NC and miR-499 inhibitor + PDCD4 siRNA groups, PDCD4 expression and the survival rate of cells were increased; and the IL-6, IL-8, IL-1β, TNF-α, NF-κB, VCAM-1, ICAM-1 and MCP-1 expression levels and the apoptosis rate were all reduced in the miR-499 inhibitor group. In the PDCD4 siRNA group, PDCD4 expression and the survival rate of cells were lower, and the expression levels of IL-6, IL-8, IL-1β, TNF-α, NF-κB, VCAM-1, ICAM-1 and MCP-1 and the apoptosis rate were all higher compared with the miR-499 mimic group. In the miR-499 inhibitor + PDCD4 siRNA group, PDCD4 expression and the survival rate of cells were higher, and the expression levels of IL-6, IL-8, IL-1β, TNF-α, NF-κB, VCAM-1, ICAM-1, and MCP-1 and the apoptosis rate were all lower than those in the PDCD4 siRNA group. Conclusion: Down-regulated miR-499 expression increased PDCD4 expression and protected endothelial cells from inflammatory damage during CAD by inhibiting the NF-κB/TNF-α signaling pathway.

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Section: Discussionsupporting

confidence: 65%

Effects of MicroRNA-499 On the Inflammatory Damage of Endothelial Cells During Coronary Artery Disease Via the Targeting of PDCD4 Through the NF-Κβ/TNF-α Signaling Pathway

Zhang¹,

He²,

Shi³

2017

Cell Physiol Biochem

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“…It is well documented that miRNAs are involved in diverse biological Page 3 of 31 A c c e p t e d M a n u s c r i p t 3 processes, including differentiation, proliferation, apoptosis, and tumorigenesis [5,6]. Depending on their specific gene or lccRNA targets, miRNAs may function as oncogenes and/or tumor suppressors [7].…”

Section: Introductionmentioning

confidence: 99%

Hsa-miR-1 suppresses breast cancer development by down-regulating K-ras and long non-coding RNA MALAT1

Liu

Lai

et al. 2015

International Journal of Biological Macromolecules

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“…The potential role(s) of miRNAs during cardiac development and their current utility in in vitro differentiation of hPSCs to heart cells are reviewed elsewhere. [164][165][166][167][168] As our knowledge broadens on miRNAs in mechanisms of heart formation, function, disease, and reprogramming or transdifferentiation, new possibilities will emerge for bioprocessing of cardiomyocytes for autologous cell therapy and novel preventive [169][170][171] and regenerative 166,172 therapeutic methods. Exosomes also emerge as vehicles for information transfer (DNA, RNA, small RNA, and proteins) among cells in the adult heart and in vitro suggesting potential roles during hPSC differentiation.…”

Section: In Vitro Methods For Cardiac Differentiation Of Hpscsmentioning

confidence: 99%

Signaling Pathways and Gene Regulatory Networks in Cardiomyocyte Differentiation

Parikh

Blanton

et al. 2015

Tissue Engineering Part B: Reviews

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Strategies for harnessing stem cells as a source to treat cell loss in heart disease are the subject of intense research. Human pluripotent stem cells (hPSCs) can be expanded extensively in vitro and therefore can potentially provide sufficient quantities of patient-specific differentiated cardiomyocytes. Although multiple stimuli direct heart development, the differentiation process is driven in large part by signaling activity. The engineering of hPSCs to heart cell progeny has extensively relied on establishing proper combinations of soluble signals, which target genetic programs thereby inducing cardiomyocyte specification. Pertinent differentiation strategies have relied as a template on the development of embryonic heart in multiple model organisms. Here, information on the regulation of cardiomyocyte development from in vivo genetic and embryological studies is critically reviewed. A fresh interpretation is provided of in vivo and in vitro data on signaling pathways and gene regulatory networks (GRNs) underlying cardiopoiesis. The state-of-the-art understanding of signaling pathways and GRNs presented here can inform the design and optimization of methods for the engineering of tissues for heart therapies.

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Small molecules, big effects: the role of microRNAs in regulation of cardiomyocyte death

Cited by 50 publications

References 194 publications

Effects of MicroRNA-499 On the Inflammatory Damage of Endothelial Cells During Coronary Artery Disease Via the Targeting of PDCD4 Through the NF-Κβ/TNF-α Signaling Pathway

Effects of MicroRNA-499 On the Inflammatory Damage of Endothelial Cells During Coronary Artery Disease Via the Targeting of PDCD4 Through the NF-Κβ/TNF-α Signaling Pathway

Hsa-miR-1 suppresses breast cancer development by down-regulating K-ras and long non-coding RNA MALAT1

Signaling Pathways and Gene Regulatory Networks in Cardiomyocyte Differentiation

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