线粒体动态蛋白MiD51在肺癌细胞增殖与凋亡中的调控作用探讨
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摘要
目的:探讨线粒体动态蛋白(mitochondrial dynamic protein of 51 kDa,MiD51)在肺癌细胞中的表达与生物学作用。方法:分别用qPCR与Western Blot实验,检测MiD51在肺癌组织中的表达。分别用MTT与克隆形成实验,检测下调MiD51表达对肺癌A549细胞增殖的影响。用流式细胞术检测下调MiD51表达对肺癌A549细胞凋亡的影响。结果:MiD51在肺癌组织中表达显著高于癌旁组织。干涉MiD51表达可抑制肺癌A549细胞的增殖与克隆形成,促进肺癌A549细胞的凋亡。结论:线粒体动态蛋白MiD51在肺癌组织中表达显著升高,进而促进肺癌细胞增殖、抑制凋亡,提示MiD51是潜在的肺癌分子治疗靶标。
Objective:To evaluate the expression of MiD51(mitochondrial dynamic protein of 51 kDa) and its biological effects in lung cancer cells.Methods:qPCR and Western Blot analysis were used to detect the expression levels of MiD51 in tumor tissues and peritumor tissues of lung cancer.The effect of MiD51 knockdown on cell proliferation was evaluated by MTT and colony formation assays in A549 cells.The effect of MiD51 knockdown on cell apoptosis was analyzed by flow cytometry in A549 cells.Results:MiD51 expression is higher in tumor tissues of the lung compared with peritumor tissues.Knockdown of MiD51 inhibited both the proliferation and colony formation of A549 cells.Knockdown of MiD51 significantly induced the apoptosis of A549 cells.Conclusion:MiD51 is overexpressed in tumor tissues of the lung,which facilitates cell proliferation and suppresses apoptosis,suggesting MiD51 as a potential therapeutic target in the treatment of lung cancer.
Objective:To evaluate the expression of MiD51(mitochondrial dynamic protein of 51 kDa) and its biological effects in lung cancer cells.Methods:qPCR and Western Blot analysis were used to detect the expression levels of MiD51 in tumor tissues and peritumor tissues of lung cancer.The effect of MiD51 knockdown on cell proliferation was evaluated by MTT and colony formation assays in A549 cells.The effect of MiD51 knockdown on cell apoptosis was analyzed by flow cytometry in A549 cells.Results:MiD51 expression is higher in tumor tissues of the lung compared with peritumor tissues.Knockdown of MiD51 inhibited both the proliferation and colony formation of A549 cells.Knockdown of MiD51 significantly induced the apoptosis of A549 cells.Conclusion:MiD51 is overexpressed in tumor tissues of the lung,which facilitates cell proliferation and suppresses apoptosis,suggesting MiD51 as a potential therapeutic target in the treatment of lung cancer.
引文
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[3]Milane L,Trivedi M,Singh A,et al.Mitochondrial biology,targets,and drug delivery[J].Journal of Controlled Release:Official Journal of the Controlled Release Society,2015,207:40-58.
[4]Ni HM,Williams JA,Ding WX.Mitochondrial dynamics and mitochondrial quality control[J].Redox Biology,2015,4:6-13.
[5]Von Stockum S,Nardin A,Schrepfer E,et al.Mitochondrial dynamics and mitophagy in Parkinson's disease:A fly point of view[J].Neurobiology of Disease,2016,90:58-67.
[6]Vasquez-Trincado C,Garcia-Carvajal I,Pennanen C,et al.Mitochondrial dynamics,mitophagy and cardiovascular disease[J].The Journal of Physiology,2016,594(3):509-525.
[7]Maassen JA,LM TH,Van Essen E,et al.Mitochondrial diabetes:Molecular mechanisms and clinical presentation[J].Diabetes,2004,53 Suppl 1:S103-S109.
[8]Serasinghe MN,Chipuk JE.Mitochondrial fission in human diseases[J].Handb Exp Pharmacol,2017,240:159-188.
[9]Mishra P,Chan DC.Mitochondrial dynamics and inheritance during cell division,development and disease[J].Nature Reviews Molecular Cell Biology,2014,15(10):634-646.
[10]Maycotte P,Marin-Hernandez A,Goyri-Aguirre M,et al.Mitochondrial dynamics and cancer[J].Tumour Biology:The Journal of the Lnternational Society for Oncodevelopmental Biology and Medicine,2017,39(5):1010428317698391.
[11]Prieto J,Torres J.Mitochondrial dynamics:In cell reprogramming as it is in cancer[J].Stem Cells International,2017,2017:8073721.
[12]Palmer CS,Osellame LD,Laine D,et al.Mi D49 and Mi D51,new components of the mitochondrial fission machinery[J].EMBO Reports,2011,12(6):565-573.
[13]Liu T,Yu R,Jin SB,et al.The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics[J].Experimental Cell Research,2013,319(18):2893-2904.
[14]Kasahara A,Scorrano L.Mitochondria:From cell death executioners to regulators of cell differentiation[J].Trends in Cell Biology,2014,24(12):761-770.
[15]Lee H,Yoon Y.Mitochondrial fission and fusion[J].Biochemical Society Transactions,2016,44(6):1725-1735.
[16]van der Bliek AM,Shen Q,Kawajiri S.Mechanisms of mitochondrial fission and fusion[J].Cold Spring Harbor Perspectives in Biology,2013,5(6):a011072.
[17]Palmer CS,Elgass KD,Parton RG,et al.Adaptor proteins Mi D49and Mi D51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission[J].The Journal of Biological Chemistry,2013,288(38):27584-27593.
[18]Trotta AP,Chipuk JE.Mitochondrial dynamics as regulators of cancer biology[J].Cellular and Molecular Life Sciences:CMLS,2017,74(11):1999-2017.
[19]Huang Q,Zhan L,Cao H,et al.Increased mitochondrial fission promotes autophagy and hepatocellular carcinoma cell survival through the ROS-modulated coordinated regulation of the NFKBand TP53 pathways[J].Autophagy,2016,12(6):999-1014.
[20]Zhan L,Cao H,Wang G,et al.Drp1-mediated mitochondrial fission promotes cell proliferation through crosstalk of p53 and NF-kappa B pathways in hepatocellular carcinoma[J].Oncotarget,2016,7(40):65001-65011.
[21]Inoue-Yamauchi A,Oda H.Depletion of mitochondrial fission factor DRP1 causes increased apoptosis in human colon cancer cells[J].Biochemical and Biophysical Research Communications,2012,421(1):81-85.
[22]Rehman J,Zhang HJ,Toth PT,et al.Inhibition of mitochondrial fission prevents cell cycle progression in lung cancer[J].FASEBJournal:Official Publication of the Federation of American Societies for Experimental Biology,2012,26(5):2175-2186.