|
|
|
|
|
MicroRNA-222 modulates the migratory ability of endothelial progenitor cells from human peripheral blood through the Akt signaling pathway
|
Xu Wen-feng, Wang Cui-ping, Zhang Hao, Cai Hua-zhong, Shi Liang, Sun Wen-wen, Ren Guo-qing
|
Department of Emergency, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China
|
|
|
Abstract Objective To explore the effects of microRNA-222(miR-222) on the migration of endothelial progenitor cells (EPCs) and the role of Akt signaling pathway and its target gene, ETS-1(ETS proto-oncogene 1, transcription factor), in this process. Methods EPCs were respectively isolated, cultured and identified from human peripheral blood. EPCs from healthy donors were transfected with miR-222 mimic, mimic negative control (NC), miR-222 inhibitor, or inhibitor NC. The expression levels of ETS-1 mRNA and miR-222 were measured by qRT-PCR. The protein levels of ETS-1, Akt and p-Akt were analyzed by western blot. The migratory ability of EPCs was assessed using Transwell assay. Results MiR-222 can regulate the expression of ETS-1 mRNA and protein. Over-expression of miR-222 significantly down-regulated the expression of ETS-1 in EPCs at the mRNA and protein levels and inhibited migratory ability of EPCs (all P<0.05). Furthermore, knockdown of miR-222 significantly up-regulated the expression of ETS-1 in EPCs at the mRNA and protein levels and promoted migratory ability of EPCs (all P<0.05). Western blot showed that up-regulation of miR-222 reduced the levels of p-Akt. Down-regulation of miR-222 increased the levels of p-Akt (all P<0.05). Conclusion MiR-222 regulated the migratory ability of EPCs via its target, EST-1, and through Akt signaling pathway.
|
|
Corresponding Authors:
Ren Guo-qing, E-mail: doctorgq@sohu.com
|
|
|
|
[1]Zuo K, Zhi K, Zhang X, et al. A dysregulated microRNA-26a/EphA2 axis impairs endothelial progenitor cell function via the p38 MAPK/VEGF pathway[J]. Cell Physiol Biochem, 2015, 35(2): 477-488.
[2]Minami Y, Satoh M, Maesawa C, et al. Effect of atorvastatin on microRNA 221/222 expression in endothelial progenitor cells obtained from patients with coronary artery disease[J]. Eur J Clin Invest, 2009, 39(5): 359-367.
[3]Zhang Q, Kandic I, Kutryk MJ. Dysregulation of angiogenesis-related microRNAs in endothelial progenitor cells from patients with coronary artery disease[J]. Biochem Biophys Res Commun, 2011, 405(1): 42-46.
[4]汪奕斌,任国庆,张浩,等. 冠心病患者外周血晚期内皮祖细胞集落数量与功能的变化[J]. 中国动脉硬化杂志, 2010, 18(2): 137-140.
[5]Wu YH, Hu TF, Chen YC, et al. The manipulation of miRNA-gene regulatory networks by KSHV induces endothelial cell motility[J]. Blood, 2011, 118(10): 2896-2905.
[6]Wang H, Qiu L, Ma Y, et al. Naoxintong inhibits myocardial infarction injury by VEGF/eNOS signaling-mediated neovascularization[J]. J Ethnopharmacol, 2017, 209: 13-23.
[7]Meng S, Cao JT, Zhang B, et al. Downregulation of microRNA-126 in endothelial progenitor cells from diabetes patients, impairs their functional properties, via target gene Spred-1[J]. J Mol Cell Cardiol, 2012, 53(1): 64-72.
[8]Liu X, Cheng Y, Yang J, et al. Cell-specific effects of miR-221/222 in vessels: molecular mechanism and therapeutic application[J]. J Mol Cell Cardiol, 2012, 52(1): 245-255.
[9]Magenta A, Ciarapica R, Capogrossi MC. The Emerging Role of miR-200 Family in Cardiovascular Diseases[J]. Circ Res, 2017, 120(9): 1399-1402.〖ZK)〗
[10]Chan YC, Roy S, Huang Y, et al. The microRNA miR-199a-5p down-regulation switches on wound angiogenesis by derepressing the v-ets erythroblastosis virus E26 oncogene homolog 1-matrix metalloproteinase-1 pathway[J]. J Biol Chem, 2012, 287(49): 41 032-41 043.
[11]张浩,孙文文,施良,等. MAPK信号通路介导血管紧张素Ⅱ对人外周血早期内皮祖细胞的功能调节[J]. 中国急救医学,2015, 35(12): 1134-1138.
[12]孙文文,任国庆,汪奕斌,等. 血管紧张素Ⅱ对外周血早期内皮祖细胞血管内皮生长因子表达的影响[J]. 中国动脉硬化杂志, 2011, 19(8): 651-654.
[13]Ihle MA, Trautmann M, Kuenstlinger H, et al. miRNA-221 and miRNA-222 induce apoptosis via the KIT/Akt signalling pathway in gastrointestinal stromal tumours[J]. Mol Oncol, 2015, 9(7): 1421-1433.
[14]Fu X, Li Y, Alvero A, et al. MicroRNA-222-3p/GNAI2/Akt axis inhibits epithelial ovarian cancer cell growth and associates with good overall survival[J]. Oncotarget, 2016, 7(49): 80 633-80 654.
[15]Li B, Lu Y, Wang H, et al. miR-221/222 enhance the tumori〖JP〗genicity of human breast cancer stem cells via modulation of PTEN/Akt pathway[J]. Biomed Pharmacother, 2016, 79: 93-101.
[16]Wong QW, Ching AK, Chan AW, et al. MiR-222 overexpression confers cell migratory advantages in hepatocellular carcinoma through enhancing Akt signaling[J]. Clin Cancer Res, 2010, 16(3): 867-875.
|
|
|
|