Wang Ying, Li Yanyan, Sun Jing, Wang Qian, Sun Cuiyun, Yan Yaping, Yu Lin, Cheng Degang, An Tongling, Shi Cuijuan, Xu Jinling, Wei Changjuan, Liu Jing, Wen Yanjun, Zhao Shujun, Li Huining, Zhang Huimin, Xu Hui, Yu Shizhu
Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
Neuroreport. 2013 Aug 21;24(12):637-45. doi: 10.1097/WNR.0b013e3283630126.
Although miR-29c has been shown to be expressed less in various kinds of solid cancers, its expression pattern and tumor-suppressive effects in gliomas remain largely unknown. In this study, we detected miR-29c in 10 nontumoral brain tissues and 60 gliomas of various grades and found that its labeling indexes were significantly lower in gliomas (53.7% for the nontumoral brain tissues, and 18.9, 5.5, and 1.8% for the WHO grade I-II, grade III, and grade IV glioma groups, respectively). We then overexpressed miR-29c in the SNB19 glioblastoma cell line and found that it markedly downregulated the expression level of CDK6, and accordingly increased the percentage of the tumor cells in the G1 phase from 44.5 to 69.1% and decreased the colony formation efficiency from 81.1 to 51.5%. miR-29c overexpression also increased the percentage of apoptotic cells from 27.2 to 54.8%, and led to a more than 50% decrease in the migratory and invasive abilities of the tumor cells. Our study shows that miR-29c can effectively block the proliferation of glioblastoma cells by inducing G1 arrest, promote their apoptosis, and inhibit their migration and invasion. At least some of its tumor-suppressive effects are mediated by specifically downregulating the expression of CDK6. Therefore, miR-29c can be used as a tumor suppressor in the gene therapy of malignant gliomas.
尽管已显示miR-29c在各种实体癌中的表达较低,但其在胶质瘤中的表达模式和肿瘤抑制作用仍 largely未知。在本研究中,我们在10个非肿瘤脑组织和60个不同级别的胶质瘤中检测了miR-29c,发现其标记指数在胶质瘤中显著降低(非肿瘤脑组织为53.7%,世界卫生组织I-II级、III级和IV级胶质瘤组分别为18.9%、5.5%和1.8%)。然后我们在SNB19胶质母细胞瘤细胞系中过表达miR-29c,发现它显著下调了CDK6的表达水平,相应地使处于G1期的肿瘤细胞百分比从44.5%增加到69.1%,并使集落形成效率从81.1%降低到51.5%。miR-29c过表达还使凋亡细胞百分比从27.2%增加到54.8%,并导致肿瘤细胞的迁移和侵袭能力下降超过50%。我们的研究表明,miR-29c可通过诱导G1期阻滞有效阻断胶质母细胞瘤细胞的增殖,促进其凋亡,并抑制其迁移和侵袭。其至少部分肿瘤抑制作用是通过特异性下调CDK6的表达介导的。因此,miR-29c可作为恶性胶质瘤基因治疗中的肿瘤抑制因子。