Long Noncoding RNA Meg3 Controls Endothelial Cell Aging and Function

Boon, Reinier A.; Hofmann, Patrick; Michalik, Katharina; Lozano-Vidal, Noelia; Berghäuser, Denise; Fischer, Ariane; Knau, Andrea; Jaé, Nicolas; Schürmann, Christoph; Dimmeler, Stefanie

doi:10.1016/j.jacc.2016.09.949

Cited by 126 publications

(95 citation statements)

References 5 publications

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“…Further investigations indicate that lncRNAs may regulate the biological processes of atherosclerosis-related endothelial cells, especially angiogenesis. For the selected examples, it has been reported that silence of lncRNA MEG3 rescued age-induced impairment of angiogenesis [10]. LncRNA SENCR has been described to be significantly upregulated in endothelial derivatives of human embryonic stem cells, and it controlled the sprouting and migratory capacity of endothelial cells [11].…”

Section: Introductionmentioning

confidence: 99%

Silence of lncRNA UCA1 Represses the Growth and Tube Formation of Human Microvascular Endothelial Cells Through miR-195

Yin

Sun

2018

Cell Physiol Biochem

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Background/Aims: Recent studies have suggested that several lncRNAs contribute to the angiogenic function of endothelial cells. Herein, we set out to reveal whether lncRNA UCA1 has functions in endothelial angiogenesis. Methods: The expression levels of lncRNA UCA1, miR-195 and CCND1 in human microvascular endothelial HMEC-1 cells were altered by transfection. Subsequently, cell viability, migration, tube formation and apoptosis of HMEC-1 cells were respectively assessed. The cross-talk between lncRNA UCA1, miR-195, CCND1, and MEK/ERK and mTOR signaling pathways were investigated by performing qRT-PCR and Western blotting. Results: Silence of lncRNA UCA1 repressed HMEC-1 cells viability, migration, tube formation, and induced apoptosis. Meanwhile, silence of lncRNA UCA1 significantly up-regulated miR-195 expression. These alterations induced by lncRNA UCA1 were further enhanced by miR-195 overexpression, while were attenuated by miR-195 suppression. Moreover, silence of lncRNA UCA1 deactivated MEK/ERK and mTOR signaling pathways via a miR-195-dependent regulation. And the deactivation of MEK/ERK and mTOR signaling pathways led to a down-regulation of CCND1. Conclusion: This study demonstrates that silence of lncRNA UCA1 largely represses microvascular endothelial cells growth and tube formation. Silence of lncRNA UCA1 exerts its function possibly via up-regulation of miR-195, which in turn inactivates MEK/ERK and mTOR signaling pathways, and ultimately represses CCND1 expression.

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Section: Introductionmentioning

confidence: 99%

Silence of lncRNA UCA1 Represses the Growth and Tube Formation of Human Microvascular Endothelial Cells Through miR-195

Yin

Sun

2018

Cell Physiol Biochem

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“…Another study also depicted a deleterious role of PA on EPCs in MetS patients via regulating lncRNA MEG3 [144]. MEG3 is required for human mesenchymal stem cells (hMSCs) differentiation into ECs [145]; however, some studies showed that MEG3 may also interfere with the proliferation and angiogenesis in VECs and its expression may correlate with cardiovascular aging [146]. These data raise a conflict of interest for which the pathophysiological roles of MEG3 needs to be studied with a deeper understanding in both EPCs and ECs.…”

Section: Role Of Ffas In Inducing Ed: Evidence From Clinical and Expementioning

confidence: 99%

Role of free fatty acids in endothelial dysfunction

et al. 2017

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Plasma free fatty acids levels are increased in subjects with obesity and type 2 diabetes, playing detrimental roles in the pathogenesis of atherosclerosis and cardiovascular diseases. Increasing evidence showing that dysfunction of the vascular endothelium, the inner lining of the blood vessels, is the key player in the pathogenesis of atherosclerosis. In this review, we aimed to summarize the roles and the underlying mechanisms using the evidence collected from clinical and experimental studies about free fatty acid-mediated endothelial dysfunction. Because of the multifaceted roles of plasma free fatty acids in mediating endothelial dysfunction, elevated free fatty acid level is now considered as an important link in the onset of endothelial dysfunction due to metabolic syndromes such as diabetes and obesity. Free fatty acid-mediated endothelial dysfunction involves several mechanisms including impaired insulin signaling and nitric oxide production, oxidative stress, inflammation and the activation of the renin-angiotensin system and apoptosis in the endothelial cells. Therefore, targeting the signaling pathways involved in free fatty acid-induced endothelial dysfunction could serve as a preventive approach to protect against the occurrence of endothelial dysfunction and the subsequent complications such as atherosclerosis.

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“…74 Because MEG3 is expressed in normal cells, the downregulation of MEG3 was investigated in various tumor types, including gastric cancer, NSCLC, and hepatocellular cancer. 75 In CRC tissues, MEG3 expression level is lower than that in the matched normal tissues and is negatively associated with tumor invasion depth, histological grade, and TNM stage. 64 …”

Section: Maternally Expressed Genementioning

confidence: 94%

Long non-coding RNAs: New biomarkers for prognosis and diagnosis of colon cancer

Deng

Wang

et al. 2017

Tumour Biol.

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BackgroundColorectal cancer (CRC) is the third most diagnosed cancer in this blue planet, whose incidence is increasing in young adults, especially in the developing countries. 1 As the fourth main cause of cancer-related deaths in the world, CRC contributes to a serious threat to human health. To descend mortality of CRC, in past decades, researchers strive to study the mechanisms of this disease. Unfortunately, the prognosis of this malignancy remains pessimistic in numerous patients who even received surgery, and the cancer reappear or metastasis come up after several months. One of the leading challenges of this disease is the clinical diagnosis may be late. 2 Therefore, biological biomarkers for the identification of detection and prediction may have clinical significance. Especially, in past decade, extensive molecular research has demonstrated that long non-coding RNAs (lncRNAs) may be novel and significant biological biomarkers for early diagnosis and prognosis of colon cancer. 3 As its name indicates, LncRNAs are a group of noncoding RNA molecules whose lengths are larger than 200 nucleotides and lack protein-coding capability.

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Long Noncoding RNA Meg3 Controls Endothelial Cell Aging and Function

Cited by 126 publications

References 5 publications

Silence of lncRNA UCA1 Represses the Growth and Tube Formation of Human Microvascular Endothelial Cells Through miR-195

Silence of lncRNA UCA1 Represses the Growth and Tube Formation of Human Microvascular Endothelial Cells Through miR-195

Role of free fatty acids in endothelial dysfunction

Long non-coding RNAs: New biomarkers for prognosis and diagnosis of colon cancer

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