肺癌中SOX30基因对PKP2基因表达的调控Expression Regulation of PKP2 Gene by SOX30 in Lung Cancer
马帮靖;郝翔麟;韩飞;刘晋祎;曹佳;张爱华;
MA Bangjing;HAO Xianglin;HAN Fei;LIU Jinyi;CAO Jia;ZHANG Aihua;Toxicology Teaching and Research Section, School of Public Health, Guizhou Medical University;Institute of Toxicology, College of Preventive Medicine, Army Medical University;
摘要(Abstract):
目的:探讨SOX30基因与PKP2基因在肺癌中的表达调控关系。方法:利用TCGA数据库数据分析SOX30与PKP2在肺癌中的相关性,利用JASPAR数据库分析PKP2启动子区SOX30蛋白转录结合位点;利用qRT-PCR检测HBE、A549、H460、H520、H358、H1975、SPC-A1、95D、LTEP等细胞中PKP2的mRNA表达情况,采用qRT-PCR及Western Blot检测H460及H520细胞转染SOX30表达载体后对PKP2的mRNA与蛋白表达的影响,用qRT-PCR检测SOX30基因敲除小鼠肺组织中PKP2 mRNA表达情况。结果:TCGA数据库数据分析表明在肺腺癌中SOX30与PKP2表达呈正相关(n=576,r=0.156,P=0.000),PKP2启动子区存在多个SOX30转录结合位点;肺癌细胞系中PKP2 mRNA表达下调,与SOX30基因表达趋势一致;过表达SOX30后,H460细胞中PKP2 mRNA及蛋白水平显著上调(P<0.05),而H520细胞中PKP2 mRNA及蛋白水平未见显著变化;敲除SOX30后,小鼠肺组织中PKP2 mRNA表达水平显著下调。结论:SOX30是调控PKP2表达的关键分子,SOX30-PKP2可能在肺腺癌中发挥重要作用。
Objective: To explore the expression and regulation relationship between SOX30 and PKP2 gene in lung cancer, and provide information for further research. Methods: The expression data of SOX30 and PKP2 were downloaded from TCGA database, and their relationship was analyzed. The JASPAR database was used to analyze the presence of the SOX30 transcription binding sites in PKP2 promoter region. And qRT-PCR was used to measure the mRNA levels of PKP2 in HBE, 8 lung cancer cell lines and the lung tissues of SOX30(+/+)、SOX30(+/+)、SOX30(+/-)and SOX30(+/-)and SOX30(-/-) mice. Moreover, qRT-PCR and Western blot were used to measure the mRNA and protein levels of H460-SOX30 and H520-SOX30 stably transfected cells. Results: Expression of PKP2 was positively correlated with that of SOX30 in human lung adenocarcinoma(n=576,r=0.156,P=0.000), and several SOX30 binding sites were consist in the promoter region of PKP2. Moreover, the expression trend of mRNA of PKP2 was consistent with that of SOX30 in lung cancer cell lines, and the ectopic expression of SOX30 in H460 cell lines significantly increased PKP2 mRNA and protein levels, but no significant difference in H520 cell lines. Besides, knock-out of SOX30 dramatically decreased PKP2 mRNA level in the lung tissues of SOX30(-/-) mice. Moreover, qRT-PCR and Western blot were used to measure the mRNA and protein levels of H460-SOX30 and H520-SOX30 stably transfected cells. Results: Expression of PKP2 was positively correlated with that of SOX30 in human lung adenocarcinoma(n=576,r=0.156,P=0.000), and several SOX30 binding sites were consist in the promoter region of PKP2. Moreover, the expression trend of mRNA of PKP2 was consistent with that of SOX30 in lung cancer cell lines, and the ectopic expression of SOX30 in H460 cell lines significantly increased PKP2 mRNA and protein levels, but no significant difference in H520 cell lines. Besides, knock-out of SOX30 dramatically decreased PKP2 mRNA level in the lung tissues of SOX30(-/-) mice. Conclusion: SOX30 is a critical transcription factor in the expression regulation of PKP2, and SOX30-PKP2 may play an important role in lung adenocarcinoma.
关键词(KeyWords):
SOX30;PKP2;肺肿瘤;癌;基因表达;转录调控
SOX30;PKP2;lung neoplasm;carcinoma;gene expression;transcriptional regulation
基金项目(Foundation): 国家自然科学基金(81773461)
作者(Authors):
马帮靖;郝翔麟;韩飞;刘晋祎;曹佳;张爱华;
MA Bangjing;HAO Xianglin;HAN Fei;LIU Jinyi;CAO Jia;ZHANG Aihua;Toxicology Teaching and Research Section, School of Public Health, Guizhou Medical University;Institute of Toxicology, College of Preventive Medicine, Army Medical University;
DOI: 10.19367/j.cnki.1000-2707.2019.06.005
参考文献(References):
- [1] TORRE L A,BRAY F,SIEGEL R L,et al.Global cancer statistic,2012[J].Ca Cancer J Clin,2015,65(2):87-108.
- [2] CHEN W Q,ZHENG R S,ZUO T T,et al.National cancer incidence and mortality in China,2012[J].China Journal of Cancer Research,2016,(1):1-11.
- [3] CHEN W Q,ZHENG R S,ZHANG S W ,et al.Cancer incidence and mortality in China in 2013:an analysis based on urbanization level[J].China Journal of Cancer Research,2017,(1):1-10.
- [4] ZENG H,ZHENG R,GUO Y,et al.Cancer survival in China,2003-2005:a population-based study[J].Int J Cancer,2015,136(8):1921-1930.
- [5] SMITH R A,MANASSARAM-BAPTISTE D,BROOKS D,et al.Cancer screening in the United States,2015:a review of current American cancer society guidelines and current issues in cancer screening[J].Ca Cancer J Clin,2015,65(1):30-54.
- [6] HAN F,DONG Y,LIU W,et al.Epigenetic regulation of Sox30 is associated with testis development in mice[J].Plos One,2014,9(5):e97203.
- [7] FENG C A,SPILLER C,MERRINER D J,et al.SOX30 is required for male fertility in mice[J].Scientific Reports,2017,7(1):17619.
- [8] HAN F,LIU W,JIANG X,et al.SOX30,a novel epigenetic silenced tumor suppressor,promotes tumor cell apoptosis by transcriptional activating p53 in lung cancer[J].Oncogene,2015,34(33):4391-4402.
- [9] HAN F,LIU W,XIAO H,et al.High expression of SOX30 is associated with favorable survival in human lung adenocarcinoma[J].Sci Rep,2015,5:13630.
- [10]PAPAGERAKIS S,SHABANA A H,DEPONDT J,et al.Immunohistochemical localization of plakophilins (PKP1,PKP2,PKP3,and p0071) in primary oropharyngeal tumors:correlation with clinical parameters[J].Human Pathology,2003,34(6):565-572.
- [11]TAKAHASHI H,NAKATSUJI H,TAKAHASHI M,et al.Up-regulation of plakophilin-2 and down-regulation of plakophilin-3 are correlated with invasiveness in bladder cancer[J].Urology,2012,79(1):240-250.
- [12]ZHANG D,QIAN Y,LIU X,et al.Up-regulation of plakophilin-2 is correlated with the progression of glioma[J].Neuropathology,2017,37(3):207-216.
- [13]DEMIRAG G G,SULLU Y,GURGENYATAGI D,et al.Expression of plakophilins (PKP1,PKP2,and PKP3) in gastric cancers[J].Diagnostic Pathology,2011,6(1):1-7.
- [14]DEMIRAG G G,SULLU Y,YUCEL I.Expression of Plakophilins (PKP1,PKP2,and PKP3) in breast cancers[J].Medical Oncology,2012,29(3):1518-1524.
- [15]GROSSMANN K S,GRUND C,HUELSKEN J,et al.Requirement of plakophilin 2 for heart morphogenesis and cardiac junction formation[J].Journal of Cell Biology,2004,167(1):149-160.
- [16]PIEPERHOFF S,SCHUMACHER H,FRANKE W W.The area composita of adhering junctions connecting heart muscle cells of vertebrates V.the importance of plakophilin-2 demonstrated by small interference RNA-mediated knockdown in cultured rat cardiomyocytes[J].European Journal of Cell Biology,2008,87(7):399-407.
- [17]VAN TINTELEN J P,ENTIUS M M,BHUIYAN Z A,et al.Plakophilin-2 mutations are the major determinant of familial arrhythmogenic right ventricular dysplasia/cardiomyopathy[J].Circulation,2006,113(13):1650-1658.
文章评论(Comment):
|
||||||||||||||||||
|
- 马帮靖
- 郝翔麟
- 韩飞
- 刘晋祎
- 曹佳
- 张爱华
MA Bangjing- HAO Xianglin
- HAN Fei
- LIU Jinyi
- CAO Jia
- ZHANG Aihua
- Toxicology Teaching and Research Section
- School of Public Health
- Guizhou Medical University
- Institute of Toxicology
- College of Preventive Medicine
- Army Medical University
- 马帮靖
- 郝翔麟
- 韩飞
- 刘晋祎
- 曹佳
- 张爱华
MA Bangjing- HAO Xianglin
- HAN Fei
- LIU Jinyi
- CAO Jia
- ZHANG Aihua
- Toxicology Teaching and Research Section
- School of Public Health
- Guizhou Medical University
- Institute of Toxicology
- College of Preventive Medicine
- Army Medical University