Circ-CHFR modulates the proliferation, migration, and invasion of ox-LDL-induced human aorta vascular smooth muscle cells through the miR-214-3p/PAPPA axis

2021 ◽  
pp. 1-14
Author(s):  
Qianqian Lu ◽  
Ying Li ◽  
Jiaping Lou ◽  
Pingzhen Li ◽  
Yi Gu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Muscle Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Human Aorta

Circular RNAs (circRNAs) are associated with the pathogenesis of human diseases, including atherosclerosis. Here, we undertook to investigate the biological role and mechanism of circRNA E3 ubiquitin-protein ligase (circ-CHFR) in atherosclerosis. The expression levels of circ-CHFR, miR-214-3p, and pregnancy-associated plasma protein A (PAPPA) were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot in human aorta vascular smooth muscle cells (HA-VSMCs) exposed to oxidized low-density lipoprotein (ox-LDL). Cell proliferation, migration, and invasion capabilities were assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT), and transwell assays, respectively. The relationship between miR-214-3p and circ-CHFR or PAPPA was confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Our data showed that circ-CHFR was upregulated in HA-VSMCs after stimulation with ox-LDL. Downregulation of circ-CHFR inhibited the proliferation, migration, and invasion of HA-VSMCs exposed to ox-LDL. Mechanistically, circ-CHFR acted as a miR-214-3p sponge, and miR-214-3p was a molecular mediator of circ-CHFR regulation in ox-LDL-stimulated HA-VSMCs. PAPPA was a miR-214-3p target, and circ-CHFR regulated the expression of PAPPA by sponging miR-214-3p. Moreover, overexpression of miR-214-3p repressed the proliferation, migration, and invasion of ox-LDL-induced HA-VSMCs by decreasing PAPPA expression. Our findings suggest that the circ-CHFR/miR-214-3p/PAPPA axis regulates ox-LDL-induced proliferation, migration, and invasion in HA-VSMCs.

scholarly journals CircRNA DOCK1 Regulates miR-409-3p/MCL1 Axis to Modulate Proliferation and Apoptosis of Human Brain Vascular Smooth Muscle Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Xinmin Ding ◽  
Xiaolong Wang ◽  
Li Han ◽  
Zhiyu Zhao ◽  
Shuai Jia ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Human Brain ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Myeloid Cell ◽  
Muscle Cells ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Proliferation And Apoptosis

BackgroundIntracranial aneurysm is an abnormal expansion in the intracranial arteries, which is associated with growth and apoptosis of vascular smooth muscle cells. Circular RNAs (circRNAs) have implicated in the progression of intracranial aneurysms. The purpose of this paper is to study the function and mechanism of circRNA dedicator of cytokinesis 1 (circ_DOCK1) in regulating proliferation and apoptosis of human brain vascular smooth muscle cells (HBVSMCs).MethodsHBVSMCs were exposed to hydrogen peroxide (H2O2). Cell proliferation and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and flow cytometry, respectively. Circ_DOCK1, microRNA (miR)-409-3p, and myeloid cell leukemia sequence 1 (MCL1) levels were examined by quantitative reverse transcription polymerase chain reaction or western blotting. The target association was assessed by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays.ResultsExposure to H2O2 decreased proliferation and increased apoptosis of HBVSMCs. Circ_DOCK1 expression was reduced in H2O2-treated HBVSMCs. Circ_DOCK1 overexpression rescued H2O2-caused reduction of proliferation and PCNA expression and attenuated H2O2-induced apoptosis and expression of Bcl-2, Bax, and cleaved PARP. MiR-409-3p was targeted by circ_DOCK1 and upregulated in H2O2-treated HBVSMCs. MiR-409-3p upregulation mitigated the role of circ_DOCK1 in proliferation and apoptosis of H2O2-treated HBVSMCs. MCL1 was targeted via miR-409-3p and downregulated via H2O2 treatment. Circ_DOCK1 overexpression enhanced MCL1 expression via modulating miR-409-3p. MiR-409-3p knockdown weakened H2O2-induced proliferation reduction and apoptosis promotion via regulating MCL1.ConclusionCirc_DOCK1 overexpression mitigated H2O2-caused proliferation inhibition and apoptosis promotion in HBVSMCs by modulating miR-409-3p/MCL1 axis.

scholarly journals Long non-coding RNA MIAT regulates ox-LDL-induced cell proliferation, migration and invasion by miR-641/STIM1 axis in human vascular smooth muscle cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gang Ma ◽  
Shuting Bi ◽  
Pengfei Zhang
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Density Lipoprotein ◽  
Vascular Diseases ◽  
Muscle Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion

Abstract Background Atherosclerosis (AS) is a primary cause of coronary heart and vascular diseases. Long non-coding RNAs (lncRNAs) are indicated to regulate AS progression. This study aimed to reveal the biological roles of lncRNA myocardial infarction associated transcript (MIAT) in oxidized low-density lipoprotein (ox-LDL)-induced human vascular smooth muscle cells (VSMCs). Methods The RNA levels of MIAT, microRNA-641 (miR-641) and stromal interaction molecule 1 (STIM1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels were determined by western blot analysis. Cell proliferation was assessed by cell colony formation and DNA content quantitation assays. Cell migration and invasion were demonstrated by wound-healing and transwell assays. The putative binding relationships between miR-641 and MIAT or STIM1 were predicted by starbase online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. Results MIAT and STIM1 expression were substantially upregulated, whereas miR-641 expression was downregulated in ox-LDL-induced VSMCs compared with control groups. Functionally, MIAT silencing attenuated ox-LDL-induced cell proliferation, migration and invasion in VSMCs; however, these effects were impaired by miR-641 inhibitor. STIM1 overexpression also restrained miR-641-mediated impacts on cell proliferation and metastasis under ox-LDL. Mechanistically, MIAT acted as a sponge for miR-641, and miR-641 was associated with STIM1. Conclusions MIAT silencing hindered ox-LDL-induced cell proliferation, migration and invasion by downregulating STIM1 expression through binding to miR-641 in VSMCs. The mechanism provided us with a new target for AS therapy.

scholarly journals lncRNA-SNHG14 Promotes Atherosclerosis by Regulating RORα Expression through Sponge miR-19a-3p

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Baoliang Zhu ◽  
Jing Liu ◽  
Ying Zhao ◽  
Jing Yan
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Direct Interaction ◽  
Muscle Cells ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Regulatory Relationship ◽  
Vsmc Proliferation

Coronary heart disease (CHD) is the most common cardiovascular disease with high prevalence, disability, and mortality. The balance between proliferation and apoptosis of vascular smooth muscle cells (VSMCs) plays a key role in the initiation of atherosclerosis. In this study, we found a significant decrease in the expression of lncRNA-SNHG14 in atherosclerotic plaque tissues of ApoE-/- mice. Overexpression of lncRNA-SNHG14 can inhibit VSMC proliferation while promoting apoptosis. There is a potential reciprocal regulatory relationship between lncRNASNHG14 and miR-19a-3p, which inhibit each other’s expression in vascular smooth muscle cells. In addition, the luciferase reporter gene analysis results showed that there was a direct interaction between miR-19a-3p and the 3′UTR of RORα. The results of qRT-PCR showed that the level of RORα mRNA was significantly increased in the aortas treated with miR-19a-3p and SNHG14 compared with that treated with miR-19a-3p alone. In conclusion, we demonstrated that lncRNA-SNHG14 regulates the apoptosis/proliferation balance of VSMCs in atherosclerosis.

scholarly journals LncRNA SNHG12 promotes proliferation and migration of vascular smooth muscle cells via targeting miR-766-5p/ EIF5A

2020 ◽  
Author(s):  
wen liu ◽  
jianhuan che ◽  
Yan Gu ◽  
ling song ◽  
yingying Jiao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Translation Initiation Factor ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Although lncRNAs have reported to serve as potential biomarkers of atherosclerosis (AS), the role of lncRNA SNHG12 in AS are still unknown. Methods In present study, we investigated the regulatory effects of SNHG12 on human vascular smooth muscle cells (hVSMCs). RT-qPCR were employed to determine the expressions of SNHG12, miR-766-5p and eukaryotic translation initiation factor 5A (EIF5A). Cell viability was estimated via the Cell Counting Kit-8 assay. Wound healing and Transwell invasion assays were used for evaluation of hVSMCs migratory capacity. To further investigate the regulatory mechanisms, binding sites between SNHG12 and miR-766-5p, EIF5A and miR-766-5p were speculated via starBase V2.0, and validated using luciferase reporter gene assay. Results It was identified that SNHG12 was up-regulated in oxidized low-density lipoprotein (ox-LDL)-insulted hVSMCs. Silencing SNHG12 inhibited ox-LDL-induced proliferation and migration of hVSMCs. Moreover, we found that SNHG12 acted as a sponge of miR-766-5p, and miR-766-5p also interacted with EIF5A. EIF5A plasmids promoted the proliferation and migratory capacities of hVSMCs, however, shRNA-SNHG12 counteracted the facilitation of EIF5A plasmids on biological behaviors of hVSMCs. Conclusions These findings of this study demonstrated that SNHG12 facilitated the migration and invasion of hVSMCs via targeting miR-766-5p/EIF5A axis.

miR-33a-5p Inhibits the Proliferation and Migration of Vascular Smooth Muscle Cells in Atherosclerosis by Targeting S1PR1

2019 ◽  
Vol 9 (7) ◽  
pp. 943-949
Author(s):  
Jiong Li ◽  
Ning Xie ◽  
Yanzhen Wang ◽  
Yirong Gan ◽  
Zongke Kou ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Luciferase Reporter ◽  
Promote Cell Proliferation ◽  
Invasion And Migration ◽  
Arterial Walls ◽  
And Migration

Background: Atherosclerosis is determined as a chronic, complicated disease, and arterial walls were mainly composed of vascular smooth muscle cells (VSMCs). microRNAs (miRNAs) have been consistently demonstrated to be involved in VSMCs, and miR-33a-5p was reported concerning many biological functions of cells. However, the role of miR-33a-5p during atherosclerosis still unclear. Methods: In present study, human VSMCs were treated with platelet-derived growth factorbb (PDGF-bb) after transfection. The miR-33a-5p and S1PR1 expression levels were determined by qRT-PCR and/or Western blot assays. VSMCs proliferation, invasion and migration were measured by CCK-8, transwell and wound healing assays, respectively. Luciferase reporter assay was employed to validate the direct targeting of S1PR1 by miR-33a-5p. Results: The results showed that PDGF-bb treated after 24 h could promote cell proliferation and regulate the expression of miR-33a-5p and S1PR1 in VSMCs. Overexpression of miR-33a-5p inhibited proliferation, invasion and migration in PDGF-bb treated VSMCs. Furthermore, we proved that miR-33a-5p could directly target S1PR1, and miR-33a-5p mimic suppressed the expression of S1PR1 in PDGF-bb treated VSMCs. Conclusions: The results suggested that miR-33a-5p could inhibit the proliferation, invasion and migration of VSMCs via suppressed the expression of S1PR1. miR-33a-5p/S1PR1 axis may represent a potential therapeutic strategy to improve atherosclerosis.

scholarly journals Downregulation of miRNA-1-3p modulates cyclic stretch-mediated proliferation of vascular smooth muscle cells through regulation of ETS-1

2020 ◽  
Vol 72 (4) ◽  
pp. 587-598
Author(s):  
Xizhen Wang ◽  
Aihua Li ◽  
Ruikang Duan ◽  
Bin Zhang
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Collagen Type ◽  
Muscle Cells ◽  
Mechanical Stretch ◽  
Cyclic Stretch ◽  
Luciferase Reporter ◽  
Type I

Mechanical stretch modulates the proliferation of vascular smooth muscle cells (VSMCs) and plays an important role in the pathogenesis of hypertension, but the underlying mechanisms are unclear. We investigated the role of microRNA- 1-3p (miRNA-1-3p) on the proliferation of VSMCs induced by mechanical cyclic stretch. Our data show that miRNA-1-3p is downregulated in the aorta of the spontaneous hypertension rat (SHR). Pathological mechanical stretch at 15% suppressed the expression of miRNA-1-3p, calponin and SM22, but enhanced the proliferation of VSMCs as well as the expression of the V-ets erythroblastosis virus E26 oncogene homolog 1 (ETS-1), collagen type I alpha (Col-1a), collagen type III alpha (Col-3a) and elastin. Overexpression of miRNA-1-3p inhibited cell proliferation and induced the expression of calponin and SM22, but decreased the expression of ETS-1, Col-1a, Col-3a and elastin. Mechanical stretch at 15% combined with losartan treatment increased the expression of miRNA-1-3p, calponin and SM22, and decreased the expression of ETS-1, Col-1a and Col-3a. Dual luciferase reporter assays revealed ETS-1 as a direct target of miRNA-1-3p. These findings suggest that miRNA-1-3p regulates VSMC function through ETS-1 regulation during hypertension-induced vascular remodeling. MiRNA-1-3p may be a viable therapeutic target for hypertension.

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