Tumor-suppressive effects of miR-29c on gliomas.
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
24(12):637-645, August 21, 2013.
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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.
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