Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

Maternally Expressed Gene 3 Negatively Regulated Decorin to Supresse Angiogenesis, Proliferation and Migration of Endothelial Cells

Author(s): Dongwei Dai, Lei Zhang, Jin Li, Yunhai Di, Chun‘ou Tian, Jianmin Liu and Bo Hong*

Volume 23, Issue 7, 2023

Published on: 26 December, 2022

Page: [698 - 708] Pages: 11

DOI: 10.2174/1566524023666221128150800

Price: $65

Abstract

Background: Angiogenesis of tumor cells is highly associated with tumorsecreted factors and matrix proteins. However, the underlying mechanism of tumorsecreted factors and matrix proteins during angiogenesis is rarely discussed.

Objectives: This study investigated the relationship between the maternally expressed gene 3 (MEG3), a tumor-secreted growth factor, and Decorin, a tumor-secreted matrix protein, and evaluated their derivate roles in human endothelial cell development.

Methods: Human endothelial cells were transiently transfected with a plasmid expressing antisense of Decorin mRNA (shDecorin) and silencing mRNA of MEG3 (siMEG3) or MEG3 over-expressive vectors. A series of qPCR and Western blot analysis was applied to characterize the expressions of MEG3 and Decorin in all transfected cells. Moreover, scratch, Transwell, and Matrigel neovascularization assays were performed to examine three key processes of endothelial cells' angiogenesis, including tubulogenesis, proliferation, and migratory levels. In addition, the cell viability was evaluated at each step via the MTT test.

Results: The overexpression of MEG3 inhibited angiogenesis and migration of endothelial cells by preventing the expression of Decorin. At the same time, the inhibition of MEG3 via siRNA resulted in an increased expression of Decorin, enhanced tube formation levels, and promoted endothelial cell proliferation and migration. Furthermore, Decorin's knockdown suppressed the angiogenesis and migration of endothelial cells without affecting the expression of MEG3. Importantly, the stimulation of HUVEC cells with exogenous Decorin protein alleviated most phenotypes induced by the upregulation of MEG3.

Conclusion: Our study demonstrated the anti-growth effects of MEG3 on vasculogenesis and migration of endothelial cells. Thus, by blocking the expression of Decorin in HUVECs, the overexpression of MEG3 repressed their development and might potentially alleviate the ischemic stroke.

Keywords: Maternally expressed gene 3, decorin, ischemic stroke, angiogenesis, proliferation, migration, HUVEC, interplay.

« Previous
[1]
Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013; 44(3): 870-947.
[http://dx.doi.org/10.1161/STR.0b013e318284056a] [PMID: 23370205]
[2]
Tovar-y-Romo LB, Penagos-Puig A, Ramírez-Jarquín JO. Endogenous recovery after brain damage: molecular mechanisms that balance neuronal life/death fate. J Neurochem 2016; 136(1): 13-27.
[http://dx.doi.org/10.1111/jnc.13362] [PMID: 26376102]
[3]
Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 2002; 8(9): 963-70.
[http://dx.doi.org/10.1038/nm747] [PMID: 12161747]
[4]
Ergul A, Alhusban A, Fagan SC. Angiogenesis. Stroke 2012; 43(8): 2270-4.
[http://dx.doi.org/10.1161/STROKEAHA.111.642710] [PMID: 22618382]
[5]
Wei R, Zhang L, Hu W, Shang X, He Y, Zhang W. Zeb2/Axin2-Enriched BMSC-derived exosomes promote post-stroke functional recovery by enhancing neurogenesis and neural plasticity. J Mol Neurosci 2022; 72(1): 69-81.
[http://dx.doi.org/10.1007/s12031-021-01887-7] [PMID: 34401997]
[6]
Zhu J, Liu S, Ye F, et al. Long Noncoding RNA MEG3 Interacts with p53 Protein and Regulates Partial p53 Target Genes in Hepatoma Cells. PLoS One 2015; 10(10): e0139790.
[http://dx.doi.org/10.1371/journal.pone.0139790] [PMID: 26444285]
[7]
Zhou Y, Zhang X, Klibanski A. MEG3 noncoding RNA: a tumor suppressor. J Mol Endocrinol 2012; 48(3): R45-53.
[http://dx.doi.org/10.1530/JME-12-0008] [PMID: 22393162]
[8]
Shen J, Zhao Z, Shang W, et al. Fabrication of a nano polymer wrapping Meg3 ShRNA plasmid for the treatment of cerebral infarction. Artificial Cells, Nanomedicine, and Biotechnology 2018; 46(S2): 894-903.
[http://dx.doi.org/10.1080/21691401.2018.1471483]
[9]
Nash MA, Loercher AE, Freedman RS. In vitro growth inhibition of ovarian cancer cells by decorin: synergism of action between decorin and carboplatin. Cancer Res 1999; 59(24): 6192-6.
[PMID: 10626812]
[10]
Kardideh B, Samimi Z, Norooznezhad F, Kiani S, Mansouri K. Autophagy, cancer and angiogenesis: where is the link? Cell Biosci 2019; 9(1): 65.
[http://dx.doi.org/10.1186/s13578-019-0327-6] [PMID: 31428311]
[11]
Lan Y, Li YJ, Li DJ, et al. Long noncoding RNA MEG3 prevents vascular endothelial cell senescence by impairing miR-128-dependent Girdin downregulation. Am J Physiol Cell Physiol 2019; 316(6): C830-43.
[http://dx.doi.org/10.1152/ajpcell.00262.2018] [PMID: 30576236]
[12]
Liu X, Hou L, Huang W, Gao Y, Lv X, Tang J. The Mechanism of Long Non-coding RNA MEG3 for Neurons Apoptosis Caused by Hypoxia: Mediated by miR-181b-12/15-LOX Signaling Pathway. Front Cell Neurosci 2016; 10: 201.
[http://dx.doi.org/10.3389/fncel.2016.00201] [PMID: 27642276]
[13]
Kwan P, Ding J, Tredget EE. MicroRNA 181b regulates decorin production by dermal fibroblasts and may be a potential therapy for hypertrophic scar. PLoS One 2015; 10(4): e0123054.
[http://dx.doi.org/10.1371/journal.pone.0123054] [PMID: 25837671]
[14]
Sofeu Feugaing DD, Götte M, Viola M. More than matrix: The multifaceted role of decorin in cancer. Eur J Cell Biol 2013; 92(1): 1-11.
[http://dx.doi.org/10.1016/j.ejcb.2012.08.004] [PMID: 23058688]
[15]
Järveläinen H, Sainio A, Wight TN. Pivotal role for decorin in angiogenesis. Matrix Biol 2015; 43: 15-26.
[http://dx.doi.org/10.1016/j.matbio.2015.01.023] [PMID: 25661523]
[16]
Lai J, Chen F, Chen J, et al. Overexpression of decorin promoted angiogenesis in diabetic cardiomyopathy via IGF1R-AKT-VEGF signaling. Sci Rep 2017; 7(1): 44473.
[http://dx.doi.org/10.1038/srep44473] [PMID: 28290552]
[17]
Schönherr E, Sunderkötter C, Schaefer L, et al. Decorin deficiency leads to impaired angiogenesis in injured mouse cornea. J Vasc Res 2004; 41(6): 499-508.
[http://dx.doi.org/10.1159/000081806] [PMID: 15528932]
[18]
Ponce ML. Tube formation: an in vitro matrigel angiogenesis assay. Methods Mol Biol 2009; 467: 183-8.
[http://dx.doi.org/10.1007/978-1-59745-241-0_10] [PMID: 19301671]
[19]
Liang CC, Park AY, Guan JL. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc 2007; 2(2): 329-33.
[http://dx.doi.org/10.1038/nprot.2007.30] [PMID: 17406593]
[20]
Madeddu P. Therapeutic angiogenesis and vasculogenesis for tissue regeneration. Exp Physiol 2005; 90(3): 315-26.
[http://dx.doi.org/10.1113/expphysiol.2004.028571] [PMID: 15778410]
[21]
Gertz K, Priller J, Kronenberg G, et al. Physical activity improves long-term stroke outcome via endothelial nitric oxide synthase-dependent augmentation of neovascularization and cerebral blood flow. Circ Res 2006; 99(10): 1132-40.
[http://dx.doi.org/10.1161/01.RES.0000250175.14861.77] [PMID: 17038638]
[22]
Staton CA, Stribbling SM, Tazzyman S, Hughes R, Brown NJ, Lewis CE. Current methods for assaying angiogenesis in vitro and in vivo. Int J Exp Pathol 2004; 85(5): 233-48.
[http://dx.doi.org/10.1111/j.0959-9673.2004.00396.x] [PMID: 15379956]
[23]
Neill T, Schaefer L, Iozzo RV. Instructive roles of extracellular matrix on autophagy. Am J Pathol 2014; 184(8): 2146-53.
[http://dx.doi.org/10.1016/j.ajpath.2014.05.010] [PMID: 24976620]
[24]
Goldoni S, Iozzo RV. Tumor microenvironment: Modulation by decorin and related molecules harboring leucine-rich tandem motifs. Int J Cancer 2008; 123(11): 2473-9.
[http://dx.doi.org/10.1002/ijc.23930] [PMID: 18798267]
[25]
Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet 2009; 10(3): 155-9.
[http://dx.doi.org/10.1038/nrg2521] [PMID: 19188922]
[26]
Peng W, Si S, Zhang Q, et al. Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate gastric cancer progression. J Exp Clin Cancer Res 2015; 34(1): 79.
[http://dx.doi.org/10.1186/s13046-015-0197-7] [PMID: 26253106]
[27]
Bi XL, Yang W. Biological functions of decorin in cancer. Chin J Cancer 2013; 32(5): 266-9.
[http://dx.doi.org/10.5732/cjc.012.10301] [PMID: 23601240]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy