MicroRNA-145 suppresses uveal melanoma angiogenesis and growth by targeting neuroblastoma RAS viral oncogene homolog and vascular endothelial growth factor

作     者：Jing-Yan Yang Yang Li Qian Wang Wen-Jia Zhou Yan-Ni Yan Wen-Bin Yang Jing-Yan;Li Yang;Wang Qian;Zhou Wen-Jia;Yan Yan-Ni;Wei Wen-Bin

作者机构：Wei Beijing Tongren Eye CenterBeijing Tongren HospitalBeijing Ophthalmology and Visual Science Key LabBeijing Key Laboratory of Intraocular Tumor Diagnosis and TreatmentCapital Medical UniversityBeijing 100730China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2020年第133卷第16期

页      面：1922-1929页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Supported by grants from the National Natural Science Foundation of China(No.81570891) Beijing Natural Science Foundation(No.7151003) Beijing Municipal Administration of Hospitals’Ascent Plan(No.DFL20150201) Advanced Health Care Professionals Development Project of Beijing Municipal Health Bureau(No.2014-2-003) The Capital Health Research and Development of Special(No.2016-1-2051) Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(No.ZYLX201307) Science&Technology Project of Beijing Municipal Science&Technology Commission(Nos.Z181100001818003 and Z151100001615052) 

主　　题：Uveal melanoma Vascular endothelial growth factor A Neuroblastoma RAS viral oncogene homolog microRNA-145 Angiogenesis 

摘      要：Background:Uveal melanoma(UM)is the most common primary intraocular malignancy in *** has been demonstrated that microRNA-145(miR-145)is correlated with the progression of various cancers by regulating the expression of multiple target genes,especially a number of genes that regulate angiogenesis and ***,the underlying mechanisms of miR-145 in tumor angiogenesis of UM are still not well ***,we aimed to explore the potential target genes or pathways regulated by miR-145 in UM and the effect of miR-145 on invasion and ***:Totally,24 choroid samples were collected in our study,including 12 UM samples and 12 normal uveal *** expression of neuroblastoma RAS viral oncogene homolog(N-RAS),phosphorylated protein kinase B(p-AKT),and vascular endothelial growth factor(VEGF)in UM tissues and normal uveal tissues was analyzed using Western blotting *** expression system was used to construct MUM-2B and OCM-1 cell lines with stable overexpression of *** and endothelial cell tube formation assay were used to measure the effects of miR-145 on the invasion and angiogenesis of UM in *** downstream target genes of miR-145 were predicted by bioinformatics and confirmed using a luciferase ***/c nude mice models were established to investigate the mechanisms of miR-145 on tumor growth and angiogenesis in *** data comparisons were performed using analysis of Student’s t test.A two-tailed P0.05 was considered as statistically ***:The results of Western blotting analysis indicated that the expressions of N-RAS(1.10±0.35 vs.0.41±0.36,t=3.997,P=0.012),p-AKT(1.16±0.22 vs.0.57±0.03,t=7.05,P=0.001),and VEGF(0.97±0.32 vs.0.45±0.21,t=3.314,P=0.008)inUMtumor tissues were significantly higher than those in normal uveal *** assay demonstrated N-RAS and VEGF as downstream targets of ***,tube formation assay revealed that miR-145-transfected human