Functional Differences of miR-125b on the Invasion of Primary Glioblastoma CD133-Negative Cells and CD133-Positive Cells

• DOI: 10.1007/s12017-012-8188-8
• Publication Date: 2012-06-18T15:57:59Z
• Authors: Lei Shi; Yi Wan; Guan Sun; Xiaoyan Gu; Chunfa Qian; Wei Yan; Shuguang Zhang; Tianhong Pan; Zhimin Wang; Yongping You
• Keywords: Adult; 0303 health sciences; Brain Neoplasms; Immunomagnetic Separation; Down-Regulation; Cell Separation; GPI-Linked Proteins; Antigens, Differentiation; Gene Expression Regulation, Neoplastic; Drug Combinations; 03 medical and health sciences; Matrix Metalloproteinase 9; Antigens, CD; Antigens, Neoplasm; Humans; Matrix Metalloproteinase 2; AC133 Antigen; Collagen; Laminin; Glioblastoma; Biomarkers; Glycoproteins

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.