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

被引：132

作者：

Zhou, Wen ^{[1
]}

Feng, Xiangling ^{[1
]}

Ren, Caiping ^{[1
]}

Jiang, Xingjun ^{[2
]}

Liu, Weidong ^{[1
]}

Huang, Wei ^{[1
]}

Liu, Zhihong ^{[3
]}

Li, Zan ^{[4
]}

Zeng, Liang ^{[3
]}

Wang, Lei ^{[1
]}

Zhu, Bin ^{[1
]}

Shi, Jia ^{[1
]}

Liu, Jie ^{[1
]}

Zhang, Chang ^{[1
]}

Liu, Yanyu ^{[1
]}

Yao, Kaitai ^{[1
,5
]}

机构：

[1] Cent S Univ, Minist Educ, Key Lab Carcinogenesis & Canc Invas Chinese,Canc, Xiang Ya Sch Med,Key Lab Carcinogenesis Chinese,M, Changsha 410078, Hunan, Peoples R China

[2] Cent S Univ, Xiangya Hosp, Dept Neurosurg, Changsha, Hunan, Peoples R China

[3] Hunan Tumor Hosp, Dept Pathol, Changsha, Hunan, Peoples R China

[4] Hunan Tumor Hosp, Dept Head & Neck Surg, Changsha, Hunan, Peoples R China

[5] Southern Med Univ, Canc Res Inst, Guangzhou, Guangdong, Peoples R China

来源：

MOLECULAR CANCER | 2013年 / 12卷

基金：

中国国家自然科学基金; 国家杰出青年科学基金;

关键词：

Nasopharyngeal carcinoma; BCAT1; c-Myc; Proliferation; Migration; Invasion; Gene amplification; Gene regulation; TUMOR-SUPPRESSOR GENE; EPIGENETIC ALTERATIONS; CANCER; INVOLVEMENT; ECA39; TSLC1; LINES; AMINOTRANSFERASES; AMPLIFICATION; HYBRIDIZATION;

D O I：

10.1186/1476-4598-12-53

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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.

引用

页数：11

共 39 条

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