SENP1、SENP2和SENP6蛋白在人恶性胶质瘤组织和细胞中的表达及其意义
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摘要
目的:观察SUMO特异性蛋白酶(SENPs)家族成员SENP1、SENP2和SENP6在人恶性胶质瘤组织和细胞中的表达,阐明其在恶性胶质瘤发生中的作用。方法:取人脑正常组织和恶性胶质瘤组织样品分别作为正常对照组和恶性胶质瘤组;培养Cos7细胞和恶性胶质瘤LN443和U343细胞,Cos7细胞作为正常细胞对照组,LN443和U343作为恶性胶质瘤细胞组;采用Western blotting法检测SENP1、SENP2和SENP6蛋白在人恶性胶质瘤组织和细胞中的表达水平。结果:在脑组织中,与正常对照组比较,恶性胶质瘤组恶性胶质瘤组织中SENP1、SENP2和SENP6蛋白表达水平均明显升高(P<0.05)。在细胞中,与正常细胞对照组比较,恶性胶质瘤细胞组LN443和U343细胞中SENP1、SENP2和SENP6蛋白表达水平均明显升高(P <0.05)。结论:SENP1、SENP2和SENP6在恶性胶质瘤组织和细胞中高表达,其可能对恶性胶质瘤的发生起到了重要的促进作用。
Objective:To observe the expressions of SENP1,SENP2 and SENP6 proteins in human malignant glioma tissue and cells,and to elucidate the their effects in the development of malignant glioma.Methods:The samples of normal human brain tissue and malignant glioma tissue were obtained and used as normal control group and malignant glioma group,respectively.The Cos7 cells and the malignant glioma LN443 and U343 cells were cultured;the Cos7 cells were used as normal cell control group,and the LN443 and U343 cells as malignant glioma cell group.Western blotting method was used to detect the expression levels of SENP1,SENP2 and SENP6 proteins in human malignant glioma tissue and cells.Results:In brain tissue,the expression levels of SENP1,SENP2 and SENP6 proteins in malignant glioma group were higher than those in normal control group(P<0.05).Compared with normal cell control group,the expression levels of SENP1,SENP2 and SENP6 proteins in the LN443 and U343 cells in malignant glioma cell group were significantly increased(P<0.05).Conclusion:SENP1,SENP2 and SENP6 proteins highly express in the malignant glioma tissue and cells,and they may play an important role in promoting the occurrence of malignant glioma.
Objective:To observe the expressions of SENP1,SENP2 and SENP6 proteins in human malignant glioma tissue and cells,and to elucidate the their effects in the development of malignant glioma.Methods:The samples of normal human brain tissue and malignant glioma tissue were obtained and used as normal control group and malignant glioma group,respectively.The Cos7 cells and the malignant glioma LN443 and U343 cells were cultured;the Cos7 cells were used as normal cell control group,and the LN443 and U343 cells as malignant glioma cell group.Western blotting method was used to detect the expression levels of SENP1,SENP2 and SENP6 proteins in human malignant glioma tissue and cells.Results:In brain tissue,the expression levels of SENP1,SENP2 and SENP6 proteins in malignant glioma group were higher than those in normal control group(P<0.05).Compared with normal cell control group,the expression levels of SENP1,SENP2 and SENP6 proteins in the LN443 and U343 cells in malignant glioma cell group were significantly increased(P<0.05).Conclusion:SENP1,SENP2 and SENP6 proteins highly express in the malignant glioma tissue and cells,and they may play an important role in promoting the occurrence of malignant glioma.
引文
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[21]QIAN J,LUO Y,GU X,et al.Inhibition of SENP6-induced radiosensitization of human hepatocellular carcinoma cells by blocking radiation-induced NF-kappaB activation[J].Cancer Biother Radiopharm,2013,28(3):196-200.
[2]LIU K,ZHANG J,WANG H.Small ubiquitin-like modifier/sentrin-specific peptidase 1 associates with chemotherapy and is a risk factor for poor prognosis of nonsmall cell lung cancer[J].J Clin Lab Anal,2018,32(9):e22611.
[3]DE ANDRADE J P,LORENZEN A W,WU V T,et al.Targeting the SUMO pathway as a novel treatment for anaplastic thyroid cancer[J].Oncotarget,2017,8(70):114801-114815.
[4]YANG Y,XIA Z,WANG X,et al.Small-molecule inhibitors targeting protein SUMOylation as novel anticancer compounds[J].Mol Pharmacol,2018,94(2):885-894.
[5]齐玲,王玮瑶,郑中华,等.SUMO及SUMO化修饰蛋白在恶性胶质瘤发生中的作用[J].吉林大学学报:医学版,2016,42(1):7-10.
[6]DONG B,GAO Y,KANG X,et al.SENP1 promotes proliferation of clear cell renal cell carcinoma through activation of glycolysis[J].Oncotarget,2016,7(49):80435-80449.
[7]JIN Z L,PEI H,XU Y H,et al.The SUMO-specific protease SENP5controls DNA damage response and promotes tumorigenesis in hepatocellular carcinoma[J].Eur Rev Med Pharmacol Sci,2016,20(17):3566-3573.
[8]MIRECKA A,MORAWIEC Z,WOZNIAK K.Genetic polymorphism of SUMO-Specific cysteine proteases-SENP1and SENP2in breast cancer[J].Pathol Oncol Res,2016,22(4):817-823.
[9]JIANG Q F,TIAN Y W,SHEN Q,et al.SENP2regulated the stability ofβ-catenin through WWOX in hepatocellular carcinoma cell[J].Tumour Biol,2014,35(10):9677-9682.
[10]齐玲,沈楠,王玮瑶,等.SENP蛋白在胶质瘤中表达与临床病理分级相关性[J].中国公共卫生,2015,31(9):1219-1221.
[11]WANG Q,XIA N,LI T,et al.SUMO-specific protease 1promotes prostate cancer progression and metastasis[J].Oncogene,2013,32(19):2493-2498.
[12]CHENG J,BAWA T,LEE P,et al.Role of desumoylation in the development of prostate cancer[J].Neoplasia,2006,8(8):667-676.
[13]XU Y,ZUO Y,ZHANG H,et al.Induction of SENP1in endothelial cells contributes to hypoxia-driven VEGFexpression and angiogenesis[J].J Biol Chem,2010,285(47):36682-36688.
[14]WANG R T,ZHI X Y,ZHANG Y,et al.Inhibition of SENP1induces radiosensitization in lung cancer cells[J].Exp Ther Med,2013,6(4):1054-1058.
[15]ZHANG Q S,ZHANG M,HUANG X J,et al.Downregulation of SENP1inhibits cell proliferation,migration and promotes apoptosis in human glioma cells[J].Oncol Lett,2016,12(1):217-221.
[16]MA C,WU B,HUANG X,et al.SUMO-specific protease 1regulates pancreatic cancer cell proliferation and invasion by targeting MMP-9[J].Tumour Biol,2014,35(12):12729-12735.
[17]TAN M Y,MU X Y,LIU B,et al.SUMO-specific protease2suppresses cell migration and invasion through inhibiting the expression of MMP13in bladder cancer cells[J].Cell Physiol Biochem,2013,32(3):542-548.
[18]HU X Y,LIU Z,ZHANG K L,et al.SUMO-specific protease 2-mediated deSUMOylation is required for NDRG2stabilization in gastric cancer cells[J].Cancer Biomark,2017,21(1):195-201.
[19]SHEN H J,ZHU H Y,YANG C,et al.SENP2regulates hepatocellular carcinoma cell growth by modulating the stability of beta-catenin[J].Asian Pac J Cancer Prev,2012,13(8):3583-3587.
[20]FU J,YU H M,CHIU S Y,et al.Disruption of SUMO-specific protease 2 induces mitochondria mediated neurodegeneration[J].PLoS Genet,2014,10(10):e1004579.
[21]QIAN J,LUO Y,GU X,et al.Inhibition of SENP6-induced radiosensitization of human hepatocellular carcinoma cells by blocking radiation-induced NF-kappaB activation[J].Cancer Biother Radiopharm,2013,28(3):196-200.