MicroRNA-370 suppresses the progression and proliferation of human astrocytoma and glioblastoma by negatively regulating β-catenin and causing activation of FOXO3a
MicroRNA-370 suppresses the progression and proliferation of human astrocytoma and glioblastoma by negatively regulating β-catenin and causing activation of FOXO3a
复制标题
DOI：
10.3892/etm.2017.5494
复制
发表时间：
2018-01-01
影响因子：
2.7
通讯作者：
Zhu, Yufang
中科院分区：
文献类型：
--
作者：
Lu, Ming;Wang, Yong;Zhu, Yufang
某些微小RNA（miR）调节各种癌症类型的进展和转移。在本研究中，评估了miR-370在人星形细胞瘤和胶质母细胞瘤细胞的进展和增殖中的作用，并研究了潜在的分子机制。采用逆转录定量PCR方法检测人脑胶质瘤及瘤旁组织中miR-370的表达。将寡核苷酸模拟物和抑制剂转染到U-251 MG人星形细胞瘤细胞系和U-87 MG胶质母细胞瘤细胞系中，并通过MTT法测定细胞活力。通过蛋白质印迹分析确定β-连环蛋白和叉头盒蛋白（FOX）O3 a的表达。结果显示，miR-370在人脑胶质瘤组织中的表达明显低于瘤旁组织。与I/II级相比，III/IV级胶质瘤患者的miR-370水平显著降低。miR-370模拟物转染抑制了U-251 MG和U-87 MG细胞的增殖。此外，miR-370水平与β-catenin呈负相关，与核FOXO 3a呈正相关。综上所述，miR-370通过调节β-catenin的水平和FOXO 3a的激活抑制人脑胶质瘤细胞的增殖，提示miR-370在人脑星形细胞瘤和胶质母细胞瘤细胞的发展中具有抑癌作用。
Certain microRNAs (miRs) regulate the progression and metastasis of various cancer types. In the present study, the role of miR-370 in the progression and proliferation of human astrocytoma and glioblastoma cells was assessed and the underlying molecular mechanism was investigated. miR-370 levels in clinical specimens of human glioma and peritumoral tissues were determined by reverse-transcription quantitative PCR. Oligonucleotide mimics and inhibitors were transfected into the U-251MG human astrocytoma cell line and the and U-87MG glioblastoma cell line and the cell viability of was determined by an MTT assay. The expression of beta-catenin and forkhead box protein (FOX) O3a was determined by western blot analysis. The results revealed that the expression of miR-370 in human glioma tissues was significantly decreased compared with that in peritumoral tissues. The miR-370 levels in patients with grade III/IV gliomas were significantly decreased compared with those in grade I/II. Transfection with miR-370 mimics inhibited the proliferation of U-251MG and U-87MG cells. Furthermore, the miR-370 levels were negatively correlated with beta-catenin and positively correlated with nuclear FOXO3a. In conclusion, miR-370 inhibited the proliferation of human glioma cells by regulating the levels of beta-catenin and the activation of FOXO3a, suggesting that miR-370 was a tumor suppressor in the progression of human astrocytoma and glioblastoma cells.