Chen Yang, Liu Wei, Chao Tengfei, Zhang Yu, Yan Xingqi, Gong Yanhua, Qiang Boqin, Yuan Jiangang, Sun Maosheng, Peng Xiaozhong
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 5 Dong Dan San Tiao, Beijing 100005, PR China.
Cancer Lett. 2008 Dec 18;272(2):197-205. doi: 10.1016/j.canlet.2008.06.034. Epub 2008 Nov 13.
MicroRNAs have been linked to different cancer-related processes. The microRNA miR-21 appears to function as an anti-apoptosis factor in glioblastomas. However, the functional target genes of miR-21 are largely unknown in glioblastomas. In this study, bioinformatics analysis was used to identify miR-21 target sites in various genes. Luciferase activity assay showed that a number of genes involved in apoptosis, PDCD4, MTAP, and SOX5, carry putative miR-21 binding sites. Expression of PDCD4 protein correlates inversely with expression of miR-21 in a number of human glioblastoma cell lines such as T98G, A172, U87, and U251. Inhibition of miR-21 increases endogenous levels of PDCD4 in cell line T98G and over-expression miR-21 inhibits PDCD4-dependent apoptosis. Together, these results indicate that miR-21 expression plays a key role in regulating cellular processes in glioblastomas and may serve as a target for effective therapies.
微小RNA与不同的癌症相关过程有关。微小RNA miR-21似乎在胶质母细胞瘤中作为一种抗凋亡因子发挥作用。然而，miR-21在胶质母细胞瘤中的功能靶基因在很大程度上尚不清楚。在本研究中，利用生物信息学分析来鉴定各种基因中的miR-21靶位点。荧光素酶活性测定表明，一些参与凋亡的基因，如PDCD4、MTAP和SOX5，携带假定的miR-21结合位点。在一些人胶质母细胞瘤细胞系如T98G、A172、U87和U251中，PDCD4蛋白的表达与miR-21的表达呈负相关。抑制miR-21可增加细胞系T98G中PDCD4的内源性水平，而过表达miR-21则抑制PDCD依赖的凋亡。总之，这些结果表明miR-21的表达在调节胶质母细胞瘤的细胞过程中起关键作用，并且可能作为有效治疗的靶点。
