Teng Hao, Wang Ping, Xue Yixue, Liu Xiaobai, Ma Jun, Cai Heng, Xi Zhuo, Li Zhen, Liu Yunhui
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China; Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang, People's Republic of China.
Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People' Republic of China.
Mol Ther. 2016 Oct;24(10):1806-1822. doi: 10.1038/mt.2016.103. Epub 2016 Jun 2.
Aberrant expression of long noncoding RNAs has recently been reported in tumorigenesis and plays a pivotal role in regulating malignant behavior of cancers. In this study, we confirmed that the long noncoding RNAs human histocompatibility leukocyte antigen (HLA) complex P5 () was up-regulated in glioma tissues as well as in U87 and U251 cells. Knockdown of inhibited the malignant biological behavior of glioma cells by reducing proliferation, migration and invasion, and inducing apoptosis. regulated the malignant behavior of glioma cells by binding to microRNA-139, which functions as a tumor suppressor. Moreover, knockdown of down-regulated Runt-related transcription factor 1, a direct and functional downstream target of microRNA-139 that is involved in microRNA-139-mediated tumor-suppressive effects in glioma cells. Runt-related transcription factor 1 increased promoter activities and upregulated expression of the oncogenic gene astrocyte elevated gene-1 (). Runt-related transcription factor 1 also increased the promoter activities and expression of , which showed a positive feedback loop in regulating the malignant behavior of glioma cells. In conclusion, this study demonstrated that the -microRNA-139- Runt-related transcription factor 1 feedback loop plays a pivotal role in regulating the malignant behavior of glioma cells, which may provide a potential therapeutic strategy for treating glioma.
最近有报道称长链非编码RNA的异常表达在肿瘤发生过程中出现,并且在调节癌症的恶性行为中起关键作用。在本研究中,我们证实长链非编码RNA人类组织相容性白细胞抗原(HLA)复合体P5()在胶质瘤组织以及U87和U251细胞中上调。敲低可通过减少增殖、迁移和侵袭以及诱导凋亡来抑制胶质瘤细胞的恶性生物学行为。通过与作为肿瘤抑制因子的微小RNA-139结合来调节胶质瘤细胞的恶性行为。此外, 敲低会下调Runt相关转录因子1,其是微小RNA-139的直接且具有功能的下游靶点,参与微小RNA-139介导的胶质瘤细胞肿瘤抑制作用。Runt相关转录因子1增加启动子活性并上调致癌基因星形细胞升高基因-1()的表达。Runt相关转录因子1还增加了的启动子活性和表达,这在调节胶质瘤细胞的恶性行为中显示出正反馈环。总之,本研究表明 -微小RNA-139-Runt相关转录因子1反馈环在调节胶质瘤细胞的恶性行为中起关键作用,这可能为治疗胶质瘤提供潜在的治疗策略。