scholarly journals miR-1290 contributes to oncogenesis and angiogenesis via targeting of THBS1, DKK3 and, SCAI

Bioimpacts ◽  
2021 ◽  
Author(s):  
Mohammad Hasan Soheilifar ◽  
Majid Pornour ◽  
Massoud Saidijam ◽  
Rezvan Najafi ◽  
Farid Azizi Jalilian ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Umbilical Vein ◽  
Wnt Signaling Pathway ◽  
Tube Formation ◽  
Luciferase Reporter ◽  
Angiogenic Potential ◽  
Umbilical Vein Endothelial Cells ◽  
Critical Process

Introduction: Colorectal cancer (CRC) is the third most common cancer in the world with high mortality, hence, understanding the molecular mechanisms involved in the tumor progression are important for CRC diagnosis and treatment. MicroRNAs (miRNAs) are key gene expression regulators that can function as tumor suppressors or oncogenes in tumor cells, and modulate angiogenesis as a critical process in tumor metastasis. MiR-1290 has been demonstrated as an onco-miRNA in various types of cancer, however, the role of miR-1290 in CRC is not fully understood. This study aimed to investigate the oncogenic and angiogenic potential of miR-1290 in CRC. Methods: Lenti-miR-1290 was transduced into HCT116, SW480, and human umbilical vein endothelial cells (HUVECs). By bioinformatics analysis, we identified thrombospondin 1 (THBS1) as a novel predicted target for miR-1290. Quantitative real-time PCR, western blotting, and luciferase reporter assay were used to demonstrate suppression of miR-1290 target genes including THBS1, Dickkopf Wnt signaling pathway inhibitor 3 (DKK3), and suppressor of cancer cell invasion (SCAI) in HCT116 and HUVECs. Cell cycle analysis, proliferation, migration and, tube formation were determined by flow cytometry, MTT, wound healing, and tube formation assays, respectively. Results: MiR-1290 significantly decreased the expression of THBS1, DKK3, and SCAI. We demonstrated that miR-1290 enhanced proliferation, migration, and angiogenesis partially through suppression of THBS1, DKK3, and SCAI in CRC. Conclusion: These results suggest a novel function of miR-1290 which may contribute to tumorigenesis and angiogenesis in CRC.

scholarly journals The Effect of MicroRNA-101 on Angiogenesis of Human Umbilical Vein Endothelial Cells during Hypoxia and in Mice with Myocardial Infarction

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Jun Pang ◽  
Liwen Ye ◽  
Qingwei Chen ◽  
Jian Wang ◽  
Xixi Yang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Target Genes ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Left Ventricular ◽  
Immunofluorescent Staining ◽  
Luciferase Reporter ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Umbilical Vein Endothelial Cells

Background. Previous studies showed that recanalization and angiogenesis within the infarct region are of vital importance to the survival of myocardial cells during the treatment of acute myocardial infarction (AMI). Methods. In this study, EdU cell proliferation assay, Transwell assay, scratch wound assay, and tube formation assay were used. Twelve bioinformatics analysis packages were used to predict the target genes of miR-101. Target genes were verified by luciferase reporter generation and assay, fluorescent quantitative PCR, and western blotting. Animal model and treatments were detected by M-mode echocardiography and immunofluorescent staining of CD31, Ki67, and α-SMA. Results. AgomiR-101 significantly enhanced HUVEC proliferation, migration, and tube formation. A double-luciferase reporter assay revealed that the hsa-miR-101 mimic attenuated the activity of the EIF4E3′-UTR-wt type plasmid by 36%. The expression levels of HIF-1α and VEGF-A in the scrambled RNA group were significantly lower than those in the EIF4E3 siRNA and agomiR-101 groups. The left ventricular ejection fraction of the AMI+Adv-miR-101 group was significantly higher than that of the AMI+Adv-null and Sham+Adv-null groups. The proliferation of vessel cells in the peripheral infarcted myocardium was higher in the AMI+Adv-miR-101 group than that in the AMI+Adv-null and Sham+Adv-null groups. Conclusion. MiR-101 can promote angiogenesis in the region surrounding the myocardial infarction.

scholarly journals SiRNA Directed Against Annexin II Receptor Inhibits Angiogenesis via Suppressing MMP2 and MMP9 Expression

2015 ◽  
Vol 35 (3) ◽  
pp. 875-884 ◽  
Author(s):  
Hongyuan Song ◽  
Dongyan Pan ◽  
Weifeng Sun ◽  
Cao Gu ◽  
Yuelu Zhang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Annexin Ii ◽  
Mmp9 Expression ◽  
Cell Arrest ◽  
Umbilical Vein Endothelial Cells

Background/Aims: Annexin II receptor (AXIIR) is able to mediate Annexin II signal and induce apoptosis, but its role in angiogenesis remains unclear. This study tries to investigate the role of AXIIR in angiogenesis and the plausible molecular mechanism. Methods/Results: RNA interference technology was used to silence AXIIR, and the subsequent effects in vitro and in vivo were evaluated thereafter. Our data indicated that human umbilical vein endothelial cells (HUVECs) expressed AXIIR and knockdown of AXIIR significantly inhibited HUVECs proliferation, adhesion, migration, and tube formation in vitro and suppressed angiogenesis in vivo. Furthermore, AXIIR siRNA induced cell arrest in the S/G2 phase while had no effect on cell apoptosis. We found that these subsequent effects might be via suppressing the expression of matrix metalloproteinase 2and matrix metalloproteinase 9. Conclusion: AXIIR participates in angiogenesis, and may be a potential therapeutic target for angiogenesis related diseases.

Abstract 103: MiR-4261 Controls Endothelial Cells Angiogenesis

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Qiulian Zhou ◽  
Dongchao Lv ◽  
Qi Sun ◽  
Ping Chen ◽  
Yihua Bei ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Heart Diseases ◽  
Umbilical Vein ◽  
Tissue Perfusion ◽  
Tube Formation ◽  
Artery Disease ◽  
Incorporation Assay ◽  
Umbilical Vein Endothelial Cells

Myocardial infarction (MI) is among major causes of morbidity and mortality associated with coronary artery disease. Angiogenesis improves tissue perfusion and cardiac repair after MI. Therefore, angiogenesis is considered to be a novel therapeutic way for ischemic heart diseases. MicroRNAs (miRNAs, miRs) have been reported to play important roles in regulating post-ischemic neovascularization. The current study aims at investigating the role of miR-4261 in angiogenesis. We found that miR-4261 mimics increased, while miR-4261 inhibitors decreased the proliferation of human umbilical vein endothelial cells (HUVEC) using EdU incorporation assay (17.25%±1.31% vs 30.91%±0.92% in nc-mimics vs mir-4261-mimics, 17.91%±1.36% vs 8.51%±0.82% in nc-inhibitor vs mir-4261-inhibitor, respectively) and CCK-8 assays (0.84±0.04 vs 1.38±0.04 in nc-mimics vs mir-4261-mimics, 0.80±0.02 vs 0.72±0.01 in nc-inhibitor vs mir-4261-inhibitor, respectively). The wound healing assay showed that miR-4261 mimic transfection resulted in a significant increase in the migration of HUVEC compared to that of the negative controls while miR-4261 inhibition had the opposite effects. Tube formation assays showed that HUVEC transfected with miR-4261 mimics increased the number of tubes formed (57.25±2.56 vs 81.5±2.53 in nc-mimics vs mir-4261-mimics, respectively), while miR-4261 inhibitor-transfected cells had the opposite effect (56.55±0.45 vs 41.38±0.52 in nc-inhibitor vs mir-4261-inhibitor, respectively). These results indicate that miR-4261 play an important role in regulating angiogenesis. However, it remains unknown which target gene mediated the effects of miR-4261. Thus, it will be of great interest to further investigate the molecular mechanisms of miR-4261 in the proliferation, migration, and tube formation of HUVEC in vitro. MiR-4261 could be a potential therapeutic target to enhance angiogenesis.

Abstract 101: MiR-4260 Promotes the Proliferation, Migration, and Tube Formation of Human Umbilical Vein Endothelial Cells

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Qi Sun ◽  
Dongcao Lv ◽  
Qiulian Zhou ◽  
Yihua Bei ◽  
Junjie Xiao
Keyword(s):  
Endothelial Cells ◽  
Target Genes ◽  
Cell Function ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Endothelial Cell Function ◽  
Human Umbilical Vein ◽  
And Migration ◽  
Umbilical Vein Endothelial Cells

MicroRNAs (miRNAs, miRs), endogenous small non-coding RNA, have been shown to act as essential regulators in angiogenesis which plays important roles in improving blood flow and cardiac function following myocardial infarction. The current study investigated the potential of miR-4260 in endothelial cell function and angiogenesis using human umbilical vein endothelial cells (HUVEC). Our data demonstrated that overexpression of miR-4260 was associated with increased proliferation and migration of HUVEC using EdU incorporation assay (17.25%±1.31 vs 25.78%±1.24 in nc-mimics vs miR-4260 mimics, respectively) and wound healing assay, respectively. While downregulation of miR-4260 inhibited the proliferation (17.90%±1.37 vs 10.66%±1.41 in nc-inhibitor vs miR-4260 inhibitor, respectively) and migration of HUVEC. Furthermore, we found that miR-4260 mimics increased (129.75±3.68 vs 147±3.13 in nc-mimics vs miR-4260 mimics, respectively), while miR-4260 inhibitor decreased the tube formation of HUVECs in vitro (123.25±2.17 vs 92±4.45 in nc-inhibitor vs miR-4260 inhibitor expression, respectively). Our data indicate that miR-4260 contributes to the proliferation, migration and tube formation of endothelial cells, and might be essential regulators for angiogenesis. Further study is needed to investigate the underlying mechanism that mediates the role of miR-4260 in angiogenesis by identifying its putative downstream target genes.

scholarly journals ATAD2 silencing decreases VEGFA secretion through targeting has-miR-520a to inhibit angiogenesis in colorectal cancer

2018 ◽  
Vol 96 (6) ◽  
pp. 761-768 ◽  
Author(s):  
Sen Hong ◽  
Si Chen ◽  
Xu Wang ◽  
Di Sun ◽  
Zhenkun Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Growth Factor Receptor ◽  
Tube Formation ◽  
Luciferase Reporter ◽  
Vascular Endothelial ◽  
Umbilical Vein Endothelial Cells ◽  
Endothelial Growth Factor

ATPase family AAA domain-containing protein 2 (ATAD2) is involved in various types of cancers, including colorectal cancer. This study aimed to determine the role of ATAD2 in angiogenesis in colorectal cancer. Here, we downregulated ATAD2 expression in HCT116 and SW480 cells, and collected the conditioned medium (CM) from control and ATAD2-silenced cells. The effect of CM on human umbilical vein endothelial cells (HUVEC) was evaluated by using CCK-8, wound healing, tube formation, Western blot, and dual-luciferase reporter assays. Our results showed that the proliferation, migration, and tube formation of HUVEC were reduced in presence of ATAD2-silenced CM, and the levels of phosphorylated vascular endothelial growth factor receptor 2 (P-VEGFR2), CD31, and CD34 were downregulated. Mechanism studies showed that ATAD2 silencing regulated the expression of vascular endothelial growth factor A (VEGFA) and miR-520a. Moreover, we found that miR-520a could bind to ATAD2, and its inhibitor partly reversed the alterations in HUVEC induced by CM from ATAD2-silenced cells. In addition, we demonstrated that miR-520a directly bound to 3′-UTR of VEGFA and inhibited its expression. Collectively, our results indicate that ATAD2 inhibition suppresses VEGFA secretion by increasing miR-520a levels. Our study suggests ATAD2 as a potential therapeutic target for angiogenesis in colorectal cancer.

scholarly journals Exosomal miR-1290 promotes angiogenesis in hepatocellular carcinoma via targeting SMEK1

2020 ◽  
Author(s):  
Qiong Wang ◽  
Guanwen Wang ◽  
Lianjie Niu ◽  
Shaorong Zhao ◽  
Jianjun Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Endothelial Cells ◽  
Tumor Angiogenesis ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Primary Liver Cancer ◽  
Tumor Model ◽  
Tube Formation ◽  
Luciferase Reporter

Abstract Background: Hepatocellular carcinoma (HCC), the most common primary liver cancer, rely on the formation of new blood vessel for growth and frequent intrahepatic and extrahepatic metastasis. Therefore, it is important to explore the underlying molecular mechanisms of tumor angiogenesis of HCC. Recently, microRNAs have been shown to modulate angiogenic processes by modulating the expression of critical angiogenic factors. However, the potential roles of tumor-derived exosomal microRNAs in regulating tumor angiogenesis remain to be elucidated. Methods: MiRNome sequencing was performed to uncover the miRNAs that are dysregulated in HCC patient serum-derived exosomes. Expression levels of miR-1290 in tissues and cells were determined by quantitative real-time PCR. The effect of mir-1290 on proliferation was evaluated by CCK-8 assay. The angiogenic ability of cells were determined by transwell, wound-healing, tube formation and matrigel plug assays. SMMC-7721 xenograft tumor model was established in NOD-SCID nude mice using miR-1290 and NC antagomirs to determin the angiogenic effect of mir-1290 in vivo. Target protein expression was determined by western blotting. Dual luciferase reporter assay was performed to confirm the action of miR-1290 on downstream target genes including SMEK1. Results are reported as means ± S.D. and differences were tested for significance using 2-sided Student’s t-test.Results: In this study, our miRNome sequencing demonstrated that miR-1290 was overexpressed in HCC patient serum-derived exosomes, and we found that delivery of miR-1290 into human endothelial cells enhanced their angiogenic ability. Our results further revealed that SMEK1 is a direct target of miR-1290 in endothelial cells. MiR-1290 exerted its pro-angiogenic function, at least in part, by alleviating the inhibition of VEGFR2 phosphorylation done by SMEK1. Conclusions: Collectively, our findings provide evidence that miR-1290 is overexpressed in HCC and promotes tumor angiogenesis via exosomal secretion, implicating its potential role as a therapeutic target for HCC.

scholarly journals Exosomes From LPS-stimulated hDPSCs Promote the Angiogenesis of HUVECs

2020 ◽  
Author(s):  
Xiangyu Huang ◽  
Wei Qiu ◽  
Yuhua Pan ◽  
Jianjia Li ◽  
Zhao Chen ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Pathway Analysis ◽  
Target Genes ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Inflammatory Factor ◽  
Vascular Regeneration ◽  
Microrna Sequencing ◽  
And Migration

Abstract Background: Angiogenesis is fundamental to biomimetic pulp regeneration. Extracellular vesicles (EVs) derived from human dental pulp stem cells (hDPSCs) from patients with periodontitis were reported to have better angiogenic capabilities. However, the underlying regulatory mechanism remains unknown. As an important component of EVs, exosomes from hDPSCs were indicated to play a crucial role in multiple regeneration processes. In this study, the inflammatory factor lipopolysaccharide (LPS) was used to stimulate hDPSCs, and exosomes were extracted from these hDPSCs. The role of exosomes in the angiogenesis of Human Umbilical Vein Endothelial Cells (HUVECs) was examined, and the underlying mechanism was studied.Method: Exosomes were isolated from hDPSCs with or without LPS stimulation. The angiogenic capabilities of HUVECs were evaluated after coculture with exosomes derived from hDPSCs (hDPSC-EXOs) or exosomes derived from LPS-stimulated hDPSCs (LPS-hDPSC-EXOs). Tube formation and migration assays were conducted, and angiogenesis-related mRNA expression was detected. MicroRNA sequencing was performed to explore the microRNA profile of hDPSC-EXOs and LPS-hDPSC-EXOs. Gene Ontology (GO) analysis was used to study the functions of the predicted target genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to estimate the signaling pathways associated with the inflammation-induced angiogenesis process.Result: The release of hDPSC-EXOs increased after stimulation with LPS. Compared to endocytosis of hDPSC-EXOs, endocytosis of LPS-hDPSC-EXOs promoted the tube formation and migration of HUVECs. The mRNA expression levels of vascular endothelial growth factor (VEGF) and kinase-insert domain-containing receptor (KDR) in the LPS-hDPSC-EXOs group were significantly higher than those in the hDPSC-EXOs group. MicroRNA sequencing showed that 10 microRNAs were significantly changed in LPS-hDPSC-EXOs; of these microRNAs, 7 were increased, and 3 were decreased. Pathway analysis showed that the genes targeted by differentially expressed microRNAs were involved in multiple angiogenesis-related pathways.Conclusion: This study revealed that exosomes derived from inflammatory hDPSCs displayed a stronger effect on vascular regeneration. It’s the first time to explore the role of exosomal microRNA from hDPSCs in inflammation-induced angiogenesis. This finding sheds new light on the effect of inflammation-stimulated hDPSCs on tissue regeneration.

scholarly journals The Impact of Simulated Weightlessness on Endothelium-Dependent Angiogenesis and the Role of Caveolae/Caveolin-1

2016 ◽  
Vol 38 (2) ◽  
pp. 502-513 ◽  
Author(s):  
Fei Shi ◽  
Tian-Zhi Zhao ◽  
Yong-Chun Wang ◽  
Xin-Sheng Cao ◽  
Chang-Bin Yang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Microgravity Environment ◽  
Caveolin 1 ◽  
Endothelial Functions ◽  
Umbilical Vein Endothelial Cells ◽  
The Impact

Background/Aims: The potential role of caveolin-1 in modulating angiogenesis in microgravity environment is unexplored. Methods: Using simulated microgravity by clinostat, we measured the expressions and interactions of caveolin-1 and eNOS in human umbilical vein endothelial cells. Results: We found that decreased caveolin-1 expression is associated with increased expression and phosphorylation levels of eNOS in endothelial cells stimulated by microgravity, which causes a dissociation of eNOS from caveolin-1 complexes. As a result, microgravity induces cell migration and tube formation in endothelial cell in vitro that depends on the regulations of caveolin-1. Conclusion: Our study provides insight for the important endothelial functions in altered gravitational environments.

MSCs inhibits the angiogenesis of HUVECs through the miR-211/Prox1 pathway

2019 ◽  
Vol 166 (1) ◽  
pp. 107-113 ◽  
Author(s):  
Jian Pan ◽  
Xianglong Wang ◽  
Dequan Li ◽  
Jianmin Li ◽  
Zipei Jiang
Keyword(s):  
Umbilical Vein ◽  
Critical Role ◽  
Corneal Opacity ◽  
Corneal Neovascularization ◽  
Inhibitory Effect ◽  
Tube Formation ◽  
Prox1 Expression ◽  
Umbilical Vein Endothelial Cells

Abstract The aim of this study was to investigate the effect of mesenchymal stem cells (MSCs) on the angiogenesis of human umbilical vein endothelial cells (HUVECs). MSCs were subconjunctival injected into rat corneal alkali burn models. Their impacts on the degree of corneal neovascularization (CNV) and corneal opacity were evaluated at 3, 6, 9 and 12 days after injection. An in vitro experiment of MSCs affecting HUVECs angiogenesis was performed and evaluated using the tube formation assay. The results showed that both CNV and corneal opacity were decreased in rats after MSCs injection. In HUVECs, angiogenesis of cells was inhibited by miR-211 overexpression. miR-211 negatively regulated Prox1 expression. Knockdown of miR-211 blocked the decrease of Prox1 expression induced by MSCs and the inhibitory effect of MSCs on the angiogenesis of HUVECs. The critical role of miR-211 in MSCs inhibition of corneal angiogenesis was confirmed in rat experiments. We concluded that MSCs inhibited the angiogenesis of HUVEC through miR-211 mediating the down-regulation of Prox1.

MicroRNA 299-3p modulates replicative senescence in endothelial cells

2013 ◽  
Vol 45 (7) ◽  
pp. 256-267 ◽  
Author(s):  
Hui-Lan Jong ◽  
Mohd Rais Mustafa ◽  
Paul M. Vanhoutte ◽  
Sazaly AbuBakar ◽  
Pooi-Fong Wong
Keyword(s):  
Endothelial Cells ◽  
Target Genes ◽  
Replicative Senescence ◽  
Umbilical Vein ◽  
Gene Profiling ◽  
Cellular Processes ◽  
Migration Capacity ◽  
Umbilical Vein Endothelial Cells ◽  
Insight Into

MicroRNAs (miRNAs) regulate various cellular processes. While several genes associated with replicative senescence have been described in endothelial cells, miRNAs that regulate these genes remain largely unknown. The present study was designed to identify miRNAs associated with replicative senescence and their target genes in human umbilical vein endothelial cells (HUVECs). An integrated miRNA and gene profiling approach revealed that hsa-miR-299-3p is upregulated in senescent HUVECs compared with the young cells, and one of its target genes could be IGF1. IGF1 was upregulated in senescent compared with young HUVECs, and knockdown of hsa-miR-299-3p dose-dependently increased the mRNA expression of IGF1, more significantly observed in the presenescent cells ( passage 19) compared with the senescent cells ( passage 25). Knockdown of hsa-miR-299-3p also resulted in significant reduction in the percentage of cells positively stained for senescence-associated β-galactosidase and increases in cell viability measured by MTT assay but marginal increases in cell proliferation and cell migration capacity measured by real-time growth kinetics analysis. Moreover, knockdown of hsa-miR-299-3p also increased proliferation of cells treated with H2O2 to induce senescence. These findings suggest that hsa-miR-299-3p may delay or protect against replicative senescence by improving the metabolic activity of the senesced cells but does not stimulate growth of the remaining cells in senescent cultures. Hence, these findings provide an early insight into the role of hsa-miR-299-3p in the modulation of replicative senescence in HUVECs.

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