文章摘要
景鹏宇,赵 楠,朱喜明,党海舟,王晓东.miR-204通过抑制OGT的表达调控非小细胞肺癌细胞的增殖和迁移[J].,2019,19(22):4220-4227
miR-204通过抑制OGT的表达调控非小细胞肺癌细胞的增殖和迁移
miR-204 Regulates the Proliferation and Metastasis of NSCLC Via Inhibiting OGT Expression
投稿时间:2019-06-12  修订日期:2019-06-30
DOI:10.13241/j.cnki.pmb.2019.22.004
中文关键词: 非小细胞肺癌  增殖  转移  miR-204  OGT
英文关键词: Non-small cell lung cancer  Proliferation  Metastasis  miR-204  OGT
基金项目:国家自然科学基金项目(81372510)
作者单位E-mail
景鹏宇 空军军医大学第二附属医院胸外科 陕西 西安 710038 jingpengyu163@163.com 
赵 楠 西安医学院公共卫生系 陕西 西安 710021  
朱喜明 空军军医大学第二附属医院胸外科 陕西 西安 710038  
党海舟 空军军医大学第二附属医院胸外科 陕西 西安 710038  
王晓东 空军军医大学第二附属医院胸外科 陕西 西安 710038  
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中文摘要:
      摘要 目的:探究miR-204和O-连接N-乙酰氨基葡萄糖转移酶(O link N-acetylglucosamine transferase,OGT)对非小细胞肺癌(Non-small cell lung cancer,NSCLC)细胞增殖和转移的影响,并深入分析其可能机制。方法:采用Oncomine及KM-Ploter数据库分析OGT在肺癌组织中的表达及与肺癌患者预后的关系;采用慢病毒转染人非小细胞肺癌A549及永生化人肺支气管上皮细胞BEAS-2B,分别构建OGT稳定下调和过表达的细胞系,利用CCK-8、平板克隆和裸鼠皮下成瘤实验检测细胞增殖的情况,划痕实验、Transwell实验和裸鼠尾静脉注射肺转移模型检测细胞转移的情况。利用数据库分析可能参与OGT调控的microRNA,并用双荧光素酶报告基因验证。利用TCGA数据库分析miR-204在肺癌中的表达情况,并在30例肺癌组织及其对应癌旁组织中分析miR-204与OGT之间的相关性。结果:OGT在肺癌组织中呈高表达,且与患者的不良预后相关(HR=1.22,P < 0.01);OGT的表达上调肺癌细胞的增殖和转移;miR-204可以负向调控OGT的表达,且miR-204在肺癌组织中表达水平显著低于癌旁组织,在肺癌组织中miR-204的水平与OGT的表达水平呈负相关(R2 = -0.4729,P < 0.01)。结论:在非小细胞肺癌中,miR-204的降低通过上调OGT的表达促进肺癌的增殖和转移。
英文摘要:
      ABSTRACT Objective: To investigate the effects of miR-204 and O-GlcNAc transferase (OGT) on the proliferation and metastasis of non-small cell lung cancer (NSCLC), and explore the possible mechanism. Methods: Oncomine and KM-Ploter databases were used to analyze the expression of OGT in the lung cancer and their relationship with the prognosis of lung cancer patients. The OGT expression in NSCLC cell line A549 or immortalized human lung bronchial epithelial cells BEAS-2B were stably down-regulated or up-regulated by lentivirus transfection. CCK-8 and Cloning formation assays were used to detect the cell proliferation ability. Wound healing and Transwell assays were used to detect the cell migration ability. Bioinformatics analysis were used to found the microRNAs that may be involved in the OGT expression and to be verified by Dual luciferase reporter gene assay. The expression of miR-204 in lung cancer was analyzed using TCGA database, and the correlation between miR-204 and OGT levels was analyzed in 30 lung cancer tissues and their corresponding adjacent tissues. Results: OGT was highly expressed and was associated with the poor prognosis of NSCLC(HR=1.22, P < 0.01). The high expression of OGT promoted the proliferation and metastasis of NSCLC cells; miR-204 negatively regulated the expression of OGT, and the expression level of miR-204 was lower in lung cancer tissues. The level of miR-204 in lung cancer tissues was negatively correlated with the expression level of OGT (R2 = -0.4729, P<0.01). Conclusion: OGT expression is regulated by miR-204 and promotes the proliferation and metastasis of lung cancer.
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