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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
AC133 Antigen
-
Adult
-
Antigens, CD / analysis*
-
Antigens, Differentiation / analysis*
-
Antigens, Neoplasm / analysis*
-
Biomarkers
-
Brain Neoplasms / genetics
-
Brain Neoplasms / metabolism
-
Brain Neoplasms / pathology*
-
Cell Separation
-
Collagen
-
Down-Regulation / drug effects
-
Drug Combinations
-
GPI-Linked Proteins / biosynthesis
-
GPI-Linked Proteins / genetics
-
Gene Expression Regulation, Neoplastic / drug effects
-
Glioblastoma / genetics
-
Glioblastoma / metabolism
-
Glioblastoma / pathology*
-
Glycoproteins / analysis*
-
Humans
-
Immunomagnetic Separation
-
Laminin
-
Matrix Metalloproteinase 2 / biosynthesis
-
Matrix Metalloproteinase 2 / genetics
-
Matrix Metalloproteinase 9 / biosynthesis
-
Matrix Metalloproteinase 9 / genetics
-
MicroRNAs / antagonists & inhibitors
-
MicroRNAs / biosynthesis
-
MicroRNAs / genetics
-
MicroRNAs / physiology*
-
Neoplasm Invasiveness / genetics*
-
Neoplasm Proteins / biosynthesis
-
Neoplasm Proteins / genetics
-
Neoplastic Stem Cells / chemistry
-
Neoplastic Stem Cells / metabolism*
-
Oligodeoxyribonucleotides / pharmacology
-
Peptides / analysis*
-
Primary Cell Culture
-
Proteoglycans
-
RNA, Neoplasm / antagonists & inhibitors
-
RNA, Neoplasm / biosynthesis
-
RNA, Neoplasm / genetics
-
RNA, Neoplasm / physiology*
-
Tissue Inhibitor of Metalloproteinase-3 / biosynthesis
-
Tissue Inhibitor of Metalloproteinase-3 / genetics
-
Transfection
-
Tumor Cells, Cultured / metabolism
-
Tumor Cells, Cultured / pathology
-
Up-Regulation / drug effects
Substances
-
AC133 Antigen
-
Antigens, CD
-
Antigens, Differentiation
-
Antigens, Neoplasm
-
Biomarkers
-
Drug Combinations
-
GPI-Linked Proteins
-
Glycoproteins
-
Laminin
-
MIRN125 microRNA, human
-
MicroRNAs
-
Neoplasm Proteins
-
Oligodeoxyribonucleotides
-
PROM1 protein, human
-
Peptides
-
Proteoglycans
-
RECK protein, human
-
RNA, Neoplasm
-
TIMP3 protein, human
-
Tissue Inhibitor of Metalloproteinase-3
-
matrigel
-
Collagen
-
MMP2 protein, human
-
Matrix Metalloproteinase 2
-
MMP9 protein, human
-
Matrix Metalloproteinase 9