G-B Wang1, J-H Liu, J Hu, K Xue. 1. Department of Neurosurgery, Yantaishan Hospital, Yantai, China. hwbgs5258@163.com.
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.
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 humanglioma 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 gliomaBCNU-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 gliomaBCNU-resistance is mediated through Spry2. CONCLUSIONS:miR-21 enhances the resistance of humanglioma cells to BCNU by decreasing the expression of Spry2 protein. Thus, Spry2 may be a novel therapeutic target for treating gliomaBCNU-resistance.
Authors: Marek Mazurek; Jakub Litak; Piotr Kamieniak; Ida Osuchowska; Ryszard Maciejewski; Jacek Roliński; Wiesława Grajkowska; Cezary Grochowski Journal: Int J Mol Sci Date: 2020-02-22 Impact factor: 5.923
Authors: Carlos DeOcesano-Pereira; Raquel A C Machado; Ana Marisa Chudzinski-Tavassi; Mari Cleide Sogayar Journal: Int J Mol Sci Date: 2020-04-09 Impact factor: 5.923