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Functional Differences of miR-125b on the Invasion of Primary Glioblastoma CD133-Negative Cells and CD133-Positive Cells
Authors:Lei Shi  Yi Wan  Guan Sun  Xiaoyan Gu  Chunfa Qian  Wei Yan  Shuguang Zhang  Tianhong Pan  Zhimin Wang  Yongping You
Institution:1. Department of Neurosurgery, The First People??s Hospital of Kunshan Affiliated with Jiangsu University, Suzhou, 215300, People??s Republic of China
2. Department of Neurosurgery, Suzhou Kowloon Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Suzhou, 215021, People??s Republic of China
4. Department of Neurosurgery, Fourth Affiliated Yancheng Hospital of Nantong University, Yancheng, 224000, People??s Republic of China
3. Department of Respiratory Medicine, The 454th Hospital of Chinese PLA, Nanjing, 210002, China
5. Department of Neurosurgery, Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, People??s Republic of China
6. Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People??s Republic of China
Abstract:MicroRNAs (miRNAs) are small noncoding RNAs whose function as modulators of gene expression is crucial for the proper control of cell development, differentiation, and homeostasis. The total number and composition of miRNAs expressed per cell at different stages of development varies widely, and the same miRNA may function differently at different stages of development. In this prospective study, we evaluated the function of miR-125b at different developmental stages of glioblastoma cells, such as primary glioblastoma cells and the corresponding stem cells. CD133 is an important surface marker in glioblastoma stem cells. We found that the upregulation of miR-125b had no effects on the invasion of primary glioblastoma CD133-negative cells but that it could inhibit the invasion of corresponding CD133-positive cells; however, the downregulation of miR-125b also had no effects on the invasion of primary glioblastoma CD133-negative cells but promoted the invasion of CD133-positive cells. Further research into the underlying mechanism demonstrated that the effects of miR-125b on the invasion of glioblastoma CD133-positive cells were associated with the alteration of the expression of MMPs (MMP-2 and MMP-9) and corresponding inhibitors (RECK and TIMP3). Our results demonstrate that miR-125b expression plays an essential role in the invasion of glioblastoma CD133-positive cells but not CD133-negative cells. Therefore, miR-125b may represent a novel target for therapy targeting the invasion of glioblastoma stem cells in the future.
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