...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular Cancer >Over-expression of BCAT1, a c-Myc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma
【24h】

Over-expression of BCAT1, a c-Myc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma

机译：过度表达c-Myc靶基因BCAT1诱导鼻咽癌细胞增殖，迁移和侵袭

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background Nasopharyngeal carcinoma (NPC) is a common malignant tumor in southern China and Southeast Asia, but its molecular mechanisms of pathogenesis are poorly understood. Our previous work has demonstrated that BCAT1 mRNA is over expressed in NPC and knocking down its expression in 5-8F NPC cell line can potently inhibit cell cycle progression and cell proliferation. However, the mechanism of BCAT1 up-regulation and its functional role in NPC development remain to be elucidated yet. Methods Immunohistochemistry (IHC) method was utilized to detect the expression of BCAT1 protein in NPC at different pathological stages. The roles of gene mutation, DNA amplification and transcription factor c-Myc in regulating BCAT1 expression were analyzed using PCR-sequencing, quantitative polymerase chain reaction (qPCR), IHC, ChIP and luciferase reporter system, respectively. The functions of BCAT1 in colony formation, cell migration and invasion properties were evaluated by RNA interference ( RNAi ). Results The positive rates of BCAT1 protein expression in normal epithelia, low-to-moderate grade atypical hyperplasia tissues, high-grade atypical hyperplasia tissues and NPC tissues were 23.6% (17/72), 75% (18/24 ), 88.9% (8/9) and 88.8% (71/80), respectively. Only one SNP site in exon1 was detected, and 42.4% (12/28) of the NPC tissues displayed the amplification of microsatellite loci in BCAT1 . C-Myc could directly bind to the c-Myc binding site in promoter region of BCAT1 and up-regulate its expression. The mRNA and protein of c - Myc and BCAT1 were co-expressed in 53.6% (15/28) and 59.1% (13/22) of NPC tissues, respectively, and BCAT1 mRNA expression was also down-regulated in c-Myc knockdown cell lines. In addition, BCAT1 knockdown cells demonstrated reduced proliferation and decreased cell migration and invasion abilities. Conclusions Our study indicates that gene amplification and c-Myc up-regulation are responsible for BCAT1 overexpression in primary NPC, and overexpression of BCAT1 induces cell proliferation, migration and invasion. The results suggest that BCAT1 may be a novel molecular target for the diagnosis and treatment of NPC.
机译：背景鼻咽癌（NPC）是中国南方和东南亚地区常见的恶性肿瘤，但其发病机理的分子机制尚不清楚。我们以前的工作表明BCAT1 mRNA在NPC中过表达，而在5-8F NPC细胞系中降低其表达可以有效抑制细胞周期进程和细胞增殖。但是，BCAT1上调的机制及其在NPC发育中的功能作用还有待阐明。方法采用免疫组织化学方法（IHC）检测BPC1蛋白在不同病理阶段在鼻咽癌中的表达。分别使用PCR测序，定量聚合酶链反应（qPCR），IHC，ChIP和荧光素酶报告系统分析了基因突变，DNA扩增和转录因子c-Myc在调节BCAT1表达中的作用。 BCAT1在菌落形成，细胞迁移和侵袭特性中的功能通过RNA干扰（RNAi）进行了评估。结果正常上皮，低至中度非典型增生组织，高度非典型增生组织和NPC组织中BCAT1蛋白的阳性表达率分别为23.6％（17/72），75％（18/24），88.9％ （8/9）和88.8％（71/80）。在外显子1中仅检测到一个SNP位点，并且42.4％（12/28）的NPC组织显示出BCAT1中微卫星基因座的扩增。 C-Myc可以直接与BCAT1启动子区域的c-Myc结合位点结合，并上调其表达。 c-Myc和BCAT1的mRNA和蛋白分别在鼻咽癌组织中的表达分别为53.6％（15/28）和59.1％（13/22），并且在c-Myc基因敲除中BCAT1 mRNA的表达也下调。细胞系。此外，BCAT1敲低细胞表现出减少的增殖和减少的细胞迁移和侵袭能力。结论我们的研究表明基因扩增和c-Myc上调是原发性NPC中BCAT1过表达的原因，而BCAT1的过表达诱导细胞增殖，迁移和侵袭。结果表明，BCAT1可能是诊断和治疗NPC的新型分子靶标。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号