骨肉瘤患者血清中miRNA-448的表达水平及临床意义  

miRNA-448 expression level in serum of osteosarcoma patients and its clinical significance

作　　者：高云翔 吕昌伟 付战利 黄省利[3] GAO Yunxiang;LYU Changwei;FU Zhanli;HUANG Shengli(Xi'an Jiaotong University Science Center,Shaanxi Xi'an 710061,China;Department of Orthopedics,the Affiliated Hospital of Northwest University·Xi'an No.3 Hospital,Shaanxi Xi'an 710000,China;Department of Orthopedics,the Second Affiliated Hospital of Xi'an Jiaotong University,Shaanxi Xi'an 710004,China.)

机构地区：[1]西安交通大学医学院,陕西西安710061 [2]西北大学附属医院·西安市第三医院骨外科,陕西西安710000 [3]西安交通大学第二附属医院骨外科,陕西西安710004

出　　处：《现代肿瘤医学》2021年第12期2123-2127,共5页Journal of Modern Oncology

摘　　要：目的:探讨骨肉瘤患者血清中miRNA-448的作用及意义。方法:采用qRT-PCR检测健康志愿者和骨肉瘤患者外周血miRNA-448的表达。microRNA靶基因数据库预测miRNA-448与Bcl-2基因可能的作用位点。qRT-PCR及Western blot实验分析miRNA-448对Bcl-2的靶向抑制作用。CCK8法检测对照组、miRNA-448 mimics转染组、miRNA-448 mimics和Bcl-2转染组中R-1059-D增殖情况。结果:骨肉瘤患者血清中miRNA-448表达水平明显低于健康志愿者(P<0.05),复发型骨肉瘤患者血清中miRNA-448表达水平明显低于原发型骨肉瘤患者(P<0.05),miRNA-448在血清中的表达水平与骨肉瘤病变及恶性程度呈负相关(P<0.05)。microRNA靶基因数据库预测潜在的miRNA-448靶基因为Bcl-2,miRNA-448通过结合Bcl-2的3'-UTR进而抑制Bcl-2的表达。miRNA-448可以抑制R-1059-D的增殖,而这种抑制效果可以被Bcl-2回补。ROC曲线分析显示,血清中miRNA-448表达水平可以有效区分骨肉瘤患者和健康对照组。结论:miRNA-448通过抑制Bcl-2表达促进细胞凋亡,在骨肉瘤的病理过程中起着关键作用。miRNA-448可作为一种抑癌基因成为诊断骨肉瘤的生物标志物。Objective:To explore the role and significance of miRNA-448 in serum of patients with osteosarcoma.Methods:qRT-PCR was used to detect the expression of miRNA-448 in peripheral blood of healthy volunteers and patients with osteosarcoma.MicroRNA target gene database predicted the possible action sites of miRNA-448 and Bcl-2 genes.Targeted inhibition of Bcl-2 by miRNA-448 was analyzed by qRT-PCR and Western blot.CCK8 assay was used to detect the proliferation of R-1059-D in the control group,miRNA-448 mimics transfection group,miRNA-448 mimics and Bcl-2 transfection group.Results:The expression level of miRNA-448 in the serum of patients with osteosarcoma was significantly lower than that of healthy volunteers(P<0.05),and the expression level of miRNA-448 in the serum of patients with recurrent osteosarcoma was significantly lower than that of patients with primary osteosarcoma(P<0.05),and the expression level of miRNA-448 in the serum was negatively correlated with the lesion and malignancy of osteosarcoma(P<0.05).The microRNA target gene database predicted the potential target gene of miRNA-448 was Bcl-2,and miRNA-448 inhibited the expression of Bcl-2 by binding to the 3'-UTR of Bcl-2.At the same time,we also found that miRNA-448 can inhibit the proliferation of R-1059-D,and this inhibitory effect can be supplemented by Bcl-2.In addition,ROC curve analysis showed that the expression level of miRNA-448 in serum could effectively distinguish patients with osteosarcoma from healthy controls.Conclusion:These findings suggest that miRNA-448 promotes apoptosis by inhibiting Bcl-2 expression and plays a key role in the pathological process of osteosarcoma.Therefore,miRNA-448 may become a biomarker for the diagnosis of osteosarcoma as a tumor suppressor gene.

关 键 词：miRNA-448 骨肉瘤 BCL-2 

分 类 号：R738.1[医药卫生—肿瘤]