ABSTRACT
OBJECTIVE: Gliomas are accompanied with high mortality owning to their invasive peculiarity and vulnerability to drug resistance. miR-21 is a vital oncogenic miRNA that regulates drug resistance of tumor cells. This study aims to elucidate the function of miR-21 in human glioma cells resistant to carmustine (BCNU) and to demonstrate the underlying molecular mechanism. MATERIALS AND METHODS: BCNU-sensitive cells (SWOZ2 cells) were transfected with miR-21 agomir and negative control, and BCNU-resistance cells (SWOZ2-BCNU cells) were transfected with miR-21 antagomir and negative control. The Real-time fluorescence quantitative PCR was used to detect and compare the levels of miR-21expression between SWOZ2-BCNU and SWOZ2 cells. The drug sensitivity of these cells to BCNU was determined by Cell Counting Kit-8 (CCK-8) assay. The protein expression of Spry2 was detected by Western blotting. RESULTS: The expression level of miR-21 was remarkably higher in SWOZ2-BCNU cells than that in SWOZ2 cells. The half-maximal inhibitory concentration (IC50) of BCNU was obviously higher for SWOZ2-BCNU cells than that for SWOZ2 cells. Besides, we found that aberrant expression of miR-21 in SWOZ2-BCNU cells is responsible for glioma BCNU-resistance. Consistently, Spry2 protein levels were significantly reduced in SWOZ2-BCNU as well as in miR-21 agomir-transfected cells, inversely correlated to miR-21 expression. The results of si-Spry2 co-transfection suggested that the effect of miR-21 on glioma BCNU-resistance is mediated through Spry2. CONCLUSIONS: miR-21 enhances the resistance of human glioma cells to BCNU by decreasing the expression of Spry2 protein. Thus, Spry2 may be a novel therapeutic target for treating glioma BCNU-resistance.
Subject(s)
Brain Neoplasms/pathology , Glioblastoma/pathology , Insulin-Like Growth Factor Binding Protein 2/metabolism , Membrane Proteins/metabolism , Phosphoproteins/metabolism , Transcription Factor RelA/metabolism , Brain Neoplasms/genetics , Brain Neoplasms/mortality , Cadherins/metabolism , Cell Line, Tumor , CpG Islands , Disease-Free Survival , Glioblastoma/genetics , Glioblastoma/mortality , Humans , Insulin-Like Growth Factor Binding Protein 2/antagonists & inhibitors , Insulin-Like Growth Factor Binding Protein 2/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Kaplan-Meier Estimate , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/genetics , Phosphoproteins/antagonists & inhibitors , Phosphoproteins/genetics , Protein Interaction Maps , RNA Interference , RNA, Small Interfering/metabolism , Signal Transduction , Snail Family Transcription Factors/metabolism , Vimentin/metabolismABSTRACT
We present in this paper a quantitative study of an effect, in which a low-energy free electron is captured and violently accelerated to GeV final kinetic energy by a stationary extra-high-intensity laser beam (Q0 identical witheE/m(e)omegac greater, similar100). The conditions under which this phenomenon can occur, such as the momentum range, incident angle of the incoming electron, the waist width of the laser beam, etc., have been investigated in detail.
