Hsa-Let-7g miRNA Targets Caspase-3 and Inhibits the Apoptosis Induced by ox-LDL in Endothelial Cells

Zhang, Yefei; Chen, Naiyun; Zhang, Jihao; Ya-ling, Tong

doi:10.3390/ijms141122708

Cited by 49 publications

(44 citation statements)

References 37 publications

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“…When exposed to various insults, such as oxidative stress, ECs become activated and express adhesion molecules, gradually resulting in certain pathological changes, including apoptosis and proliferation inhibition[5, 20]. Ox-LDL has been shown to be an important risk factor in the initiation and progression of atherosclerosis[21].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-497 Induces Apoptosis and Suppresses Proliferation via the Bcl-2/Bax-Caspase9-Caspase3 Pathway and Cyclin D2 Protein in HUVECs

Tang

Wang

et al. 2016

PLoS ONE

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IntroductionMicroRNAs play crucial roles in various types of diseases. However, to date, no information about the role of miR-497 in the development of atherosclerosis has been reported. This study investigated the possible role of miR-497 in vascular endothelial cell injury during the early stage of atherosclerosis.Materials and MethodsThe expression level of miR-497 in human umbilical vein endothelial cells (HUVECs) exposed to ox-LDL was detected using qRT-PCR. To perform gain of function and loss of function analyses, miR-497 mimics were transfected into HUVECs, and miR-497 inhibitors were transfected into HUVECs stimulated with ox-LDL. Flow cytometry was used to analyze cell cycle progression and apoptosis. EdU and CCK-8 assays were employed to detect DNA synthesis and cell proliferation, respectively. After bioinformatics prediction, a dual Luciferase Reporter assay was used to analyze the direct target genes of miR-497. The mRNA and protein levels of the target genes were detected using qRT-PCR and western blot analyses, respectively. Caspase-9/3 activity was analyzed to determine the mechanism of endothelial dysfunction.ResultsWe showed that miR-497 was significantly upregulated in HUVECs stimulated with ox-LDL. Ectopic expression of miR-497 suppressed cell proliferation, induced apoptosis and increased the activity of caspase-9/3. After verification, Bcl2 and CCND2 were shown to be direct target genes of miR-497 in HUVECs. MiR-497 significantly suppressed cell proliferation by arresting the cell cycle through the CCND2 protein and induced apoptosis through the Bcl2/Bax-caspase9-caspase3 pathway.ConclusionOverall, our study shows that miR-497 might play a role in the development of atherosclerosis by inducing apoptosis and suppressing the proliferation of vascular endothelial cells. Therefore, miR-497 could be a potential therapeutic target for the treatment of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-497 Induces Apoptosis and Suppresses Proliferation via the Bcl-2/Bax-Caspase9-Caspase3 Pathway and Cyclin D2 Protein in HUVECs

Tang

Wang

et al. 2016

PLoS ONE

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“…An increasing amount of experimental evidence has strongly supported that miRNAs are a critical regulator in controlling processes that underlie cell proliferation, differentiation and apoptosis in diverse organisms during normal development (Hassan et al 2012;Zhang et al 2013;Yang et al 2014). MiR-143, which was originally detected during adipocyte differentiation (Esau et al 2004), in many studies has emerged as an essential regulator of cellular physiology, particularly in tumorigenesis and cancer (Akao et al 2009;Quintavalle et al 2010;Qian et al 2013).…”

Section: Discussionmentioning

confidence: 99%

miR-143 inhibits proliferation and induces apoptosis of mammary epithelial cells in dairy goat

Wang

Hou

et al. 2016

Animal Cells and Systems

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MicroRNAs are a class of post-transcriptional regulators of gene expression in multicellular organisms, which play important roles in cell fate, organ morphogenesis and carcinogenesis. In the present study, we demonstrated the critical roles of miR-143 on mammary epithelial cells of dairy goat. The test results of cell count, methylthiazolyldiphenyl-tetrazolium bromide, Hoechst33342/PI (propidium iodide) and flow cytometry showed miR-143-induced G0/G1 phase arrest, inhibited proliferation and promoted apoptosis of mammary epithelial cells; the qRT-PCR test of marker genes related to cell proliferation and apoptosis, BAX and BCL-2, supported the same conclusions. Our study presents evidence that miR-143 is an important post-transcription regulator involving in mammary cells survival, and it may have a value function in mammary gland development, lactation or involution.ARTICLE HISTORY

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“…miR-Let-7a directly targets caspase 3 mRNA as the 3′UTR of the protein coding genes perfectly matches the seed sequence of miR-Let-7a facilitating mRNA translational repression and/or degradation. Indeed, miR-Let7a has been shown to suppress drug-induced apoptosis in cells via its regulatory effect on caspase-3 expression [25, 26]. A seminal finding of the present study was that relative expression of miR-Let-7a was markedly lower (~140%) in the endothelial cells exposed to hgEMPs compared with ngEMPs.…”

Section: Discussionmentioning

confidence: 57%

High glucose derived endothelial microparticles increase active caspase-3 and reduce microRNA-Let-7a expression in endothelial cells

Bammert

Hijmans

Reiakvam

et al. 2017

Biochemical and Biophysical Research Communications

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The experimental aim of this study was to determine the effects of high glucose-induced endothelial microparticles (EMPs) on endothelial cell susceptibility to apoptosis. Human umbilical vein endothelial cells (HUVECs) were cultured (3rd passage) and plated in 6-well plates at a density of 5.0 × 105 cells/condition. Cells were incubated with media containing 25mM D-glucose (concentration representing a diabetic glycemic state) or 5mM D-glucose (normoglycemic condition) for 48 h to generate EMPs. EMP identification (CD144+ expression) and concentration was determined by flow cytometry. HUVECs (3×106 cells/condition) were treated with EMPs generated from either the normal or high glucose conditions for 24 h. Intracellular concentration of active caspase-3 was determined by enzyme immunoassay. Cellular expression of miR-Let7a, an anti-apoptotic microRNA, was determined by RT-PCR using the ΔΔCT normalized to RNU6. High glucose-derived EMPs significantly increased both basal (1.5±0.1 vs 1.0±0.1 ng/mL) and staurosporine-stimulated (2.2±0.2 vs 1.4±0.1 ng/mL) active caspase-3 compared with normal glucose EMPs. Additionally, the expression of miR-Let-7a was markedly reduced (~140%) by high glucose EMPs (0.43±0.17 fold vs control). These results demonstrate that hyperglycemic-induced EMPs increase endothelial cell active caspase-3. This apoptotic effect may be mediated, at least in part, by a reduction in miR-Let-7a expression.

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Hsa-Let-7g miRNA Targets Caspase-3 and Inhibits the Apoptosis Induced by ox-LDL in Endothelial Cells

Cited by 49 publications

References 37 publications

MicroRNA-497 Induces Apoptosis and Suppresses Proliferation via the Bcl-2/Bax-Caspase9-Caspase3 Pathway and Cyclin D2 Protein in HUVECs

MicroRNA-497 Induces Apoptosis and Suppresses Proliferation via the Bcl-2/Bax-Caspase9-Caspase3 Pathway and Cyclin D2 Protein in HUVECs

miR-143 inhibits proliferation and induces apoptosis of mammary epithelial cells in dairy goat

High glucose derived endothelial microparticles increase active caspase-3 and reduce microRNA-Let-7a expression in endothelial cells

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