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

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• 作者：Wen Zhou (1)
  Xiangling Feng (1)
  Caiping Ren (1)
  Xingjun Jiang (2)
  Weidong Liu (1)
  Wei Huang (1)
  Zhihong Liu (3)
  Zan Li (4)
  Liang Zeng (3)
  Lei Wang (1)
  Bin Zhu (1)
  Jia Shi (1)
  Jie Liu (1)
  Chang Zhang (1)
  Yanyu Liu (1)
  Kaitai Yao (1) (5)
  
• 关键词：Nasopharyngeal carcinoma ; BCAT1 ; c ; Myc ; Proliferation ; Migration ; Invasion ; Gene amplification ; Gene regulation
• 刊名：Molecular Cancer
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：12
• 期：1
• 全文大小：1728KB
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• 作者单位：Wen Zhou (1)
  Xiangling Feng (1)
  Caiping Ren (1)
  Xingjun Jiang (2)
  Weidong Liu (1)
  Wei Huang (1)
  Zhihong Liu (3)
  Zan Li (4)
  Liang Zeng (3)
  Lei Wang (1)
  Bin Zhu (1)
  Jia Shi (1)
  Jie Liu (1)
  Chang Zhang (1)
  Yanyu Liu (1)
  Kaitai Yao (1) (5)
  
  1. Cancer Research Institute, Xiang-Ya School of Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, Key Laboratory for Carcinogenesis & Cancer Invasion of Chinese Ministry of Education, Central South University, Xiangya Road 110, 410078, Changsha, Hunan, P. R. China
  2. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China
  3. Department of Pathology, Hunan Tumor Hospital, Changsha, Hunan, P. R. China
  4. Department of Head and Neck Surgery, Hunan Tumor Hospital, Changsha, Hunan, P. R. China
  5. Cancer Research Institute, Southern Medical University, Guangzhou, Guangdong, P. R. China
  
• ISSN：1476-4598

文摘

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.