Journal of Shanghai Jiao Tong University (Medical Science) >
Whole gene expression profile analysis of miRNAs in human umbilical vein endothelial cells regulated by vascular endothelial growth factor A
Received date: 2021-01-27
Online published: 2021-08-24
Supported by
National Natural Science Foundation of China(31671503)
·To analyze the changes of microRNA (miRNA) in human umbilical vein endothelial cells (HUVECs) under the stimulation of vascular endothelial growth factor A (VEGFA), in order to further explore the roles of miRNA in regulating the expression of downstream genes of VEGFA, and to find new regulatory miRNAs for angiogenesis.
·The miRNA expression profile was analyzed by using NanoString nCounter in HUVECs 0, 1, 4, and 12 h after VEGFA stimulation. The differentially expressed miRNAs with the same trend were clustered and their target genes were predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze and predict the functions of these target genes, and the interaction networks were established.
·The expression of 39 miRNAs changed significantly after VEGFA stimulation in HUVECs. Bioinformatic analysis showed that there were 129 target mRNAs corresponding to the differentially expressed miRNAs which were involved in multiple biological processes and signal pathways related to angiogenesis.
·miRNAs are differentially expressed in HUVECs after stimulation by VEGFA, and miRNAs play important roles in regulating angiogenesis. MiR-107 and miR-21 may severe as candidate functional regulators of angiogenesis.
Li LIU , Zi-long GENG , Jia-huan CHEN , Sha-sha ZHANG , Bing ZHANG . Whole gene expression profile analysis of miRNAs in human umbilical vein endothelial cells regulated by vascular endothelial growth factor A[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2021 , 41(9) : 1183 -1189 . DOI: 10.3969/j.issn.1674-8115.2021.09.008
1 | Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis[J]. Nature, 2011, 473(7347): 298-307. |
2 | Melincovici CS, Bo?ca AB, ?u?man S, et al. Vascular endothelial growth factor (VEGF) - key factor in normal and pathological angiogenesis[J]. Revue Roumaine De Morphol et Embryol, 2018, 59(2): 455-467. |
3 | Simons M, Gordon E, Claesson-Welsh L. Mechanisms and regulation of endothelial VEGF receptor signalling[J]. Nat Rev Mol Cell Biol, 2016, 17(10): 611-625. |
4 | Chung AS, Ferrara N. Developmental and pathological angiogenesis[J]. Annu Rev Cell Dev Biol, 2011, 27: 563-584. |
5 | Claesson-Welsh L, Welsh M. VEGFA and tumour angiogenesis[J]. J Intern Med, 2013, 273(2): 114-127. |
6 | Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function[J]. Cell, 2004, 116(2): 281-297. |
7 | Michlewski G, Cáceres JF. Post-transcriptional control of miRNA biogenesis[J]. RNA, 2019, 25(1): 1-16. |
8 | Peng Y, Croce CM. The role of microRNAs in human cancer[J]. Signal Transduct Target Ther, 2016, 1: 15004. |
9 | Zhao Z, Sun W, Guo ZY, et al. Mechanisms of lncRNA/microRNA interactions in angiogenesis[J]. Life Sci, 2020, 254: 116900. |
10 | Wang SY, Chen JH, Garcia SP, et al. A dynamic and integrated epigenetic program at distal regions orchestrates transcriptional responses to VEGFA[J]. Genome Res, 2019, 29(2): 193-207. |
11 | Anders S, McCarthy DJ, Chen YS, et al. Count-based differential expression analysis of RNA sequencing data using R and Bioconductor[J]. Nat Protoc, 2013, 8(9): 1765-1786. |
12 | Blazek AD, Nam J, Gupta R, et al. Exercise-driven metabolic pathways in healthy cartilage[J]. Osteoarthritis Cartilage, 2016, 24(7): 1210-1222. |
13 | Feng YH, Tsao CJ. Emerging role of microRNA-21 in cancer[J]. Biomed Rep, 2016, 5(4): 395-402. |
14 | Luo M, Tan XY, Mu L, et al. MiRNA-21 mediates the antiangiogenic activity of metformin through targeting PTEN and SMAD7 expression and PI3K/AKT pathway[J]. Sci Rep, 2017, 7: 43427. |
15 | Celic T, Metzinger-Le Meuth V, Six I, et al. The miR-221/222 cluster is a key player in vascular biology via the fine-tuning of endothelial cell physiology[J]. Curr Vasc Pharmacol, 2017, 15(1): 40-46. |
16 | Li XH, Zhang Y, Shi YQ, et al. MicroRNA-107, an oncogene microRNA that regulates tumour invasion and metastasis by targeting DICER1 in gastric cancer[J]. J Cell Mol Med, 2011, 15(9): 1887-1895. |
17 | Chen JJ, Zhou X, Xiao QR, et al. MiR-107 suppresses cell proliferation and tube formation of Ewing sarcoma cells partly by targeting HIF-1β[J]. Hum Cell, 2018, 31(1): 42-49. |
18 | Chen L, Li ZY, Xu SY, et al. Upregulation of miR-107 inhibits glioma angiogenesis and VEGF expression[J]. Cell Mol Neurobiol, 2016, 36(1): 113-120. |
19 | Vishnoi A, Rani S. MiRNA biogenesis and regulation of diseases: an overview[J]. Methods Mol Biol, 2017, 1509: 1-10. |
20 | Hydbring P, Badalian-Very G. Clinical applications of microRNAs[J]. F1000Research, 2013, 2: 136. |
21 | Garrett-Sinha LA. Review of Ets1 structure, function, and roles in immunity[J]. Cell Mol Life Sci, 2013, 70(18): 3375-3390. |
22 | Chen J, Fu Y, Day DS, et al. VEGF amplifies transcription through ETS1 acetylation to enable angiogenesis[J]. Nat Commun, 2017, 8(1): 383. |
23 | Thum T, Gross C, Fiedler J, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAPK signalling in fibroblasts[J]. Nature, 2008, 456(7224): 980-984. |
24 | Poliseno L, Tuccoli A, Mariani L, et al. MicroRNAs modulate the angiogenic properties of HUVECs[J]. Blood, 2006, 108(9): 3068-3071. |
25 | Felli N, Fontana L, Pelosi E, et al. MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation[J]. Proc Natl Acad Sci USA, 2005, 102(50): 18081-18086. |
26 | Fiedler J, Jazbutyte V, Kirchmaier BC, et al. MicroRNA-24 regulates vascularity after myocardial infarction[J]. Circulation, 2011, 124(6): 720-730. |
27 | 李洁, 秦性良, 邵宁生. MicroRNA及其靶基因的时空特异性与动态变化[J]. 生物化学与生物物理进展, 2013, 40(7): 617-626. |
28 | Mukhopadhyay D, Knebelmann B, Cohen HT, et al. The von Hippel-Lindau tumor suppressor gene product interacts with Sp1 to repress vascular endothelial growth factor promoter activity[J]. Mol Cell Biol, 1997, 17(9): 5629-5639. |
29 | Chen Z, Lai TC, Jan YH, et al. Hypoxia-responsive miRNAs target argonaute 1 to promote angiogenesis[J]. J Clin Invest, 2013, 123(3): 1057-1067. |
30 | Chen PS, Su JL, Cha ST, et al. miR-107 promotes tumor progression by targeting the let-7 microRNA in mice and humans[J]. J Clin Invest, 2017, 127(3): 1116. |
31 | Wu Q, Yang Z, An Y, et al. MiR-19a/b modulate the metastasis of gastric cancer cells by targeting the tumour suppressor MXD1[J]. Cell Death Dis, 2014, 5: e1144. |
32 | Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis[J]. J Clin Oncol, 2005, 23(5): 1011-1027. |
33 | Shiojima I, Walsh K. Role of Akt signaling in vascular homeostasis and angiogenesis[J]. Circ Res, 2002, 90(12): 1243-1250. |
34 | Wilhelm K, Happel K, Eelen G, et al. FOXO1 couples metabolic activity and growth state in the vascular endothelium[J]. Nature, 2016, 529(7585): 216-220. |
35 | Jayson GC, Kerbel R, Ellis LM, et al. Antiangiogenic therapy in oncology: current status and future directions[J]. Lancet, 2016, 388(10043): 518-529. |
/
〈 |
|
〉 |