Over-expression of BCAT1, a c-Myc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma.
Over-expression of BCAT1, a c-Myc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma.
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DOI：
10.1186/1476-4598-12-53
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发表时间：
2013-06-08
期刊：
影响因子：
37.3
通讯作者：
Yao K
中科院分区：
文献类型：
--
作者：
Zhou W;Feng X;Ren C;Jiang X;Liu W;Huang W;Liu Z;Li Z;Zeng L;Wang L;Zhu B;Shi J;Liu J;Zhang C;Liu Y;Yao K
鼻咽癌（NPC）是中国南方和东南亚地区常见的恶性肿瘤，但其发病的分子机制尚不清楚。我们之前的工作表明，BCAT1 mRNA 在 NPC 中过度表达，敲低其在 5-8F NPC 细胞系中的表达可以有效抑制细胞周期进程和细胞增殖。然而，BCAT1上调的机制及其在NPC发育中的功能作用仍有待阐明。采用免疫组织化学（IHC）方法检测鼻咽癌不同病理阶段BCAT1蛋白的表达情况。分别使用PCR测序、定量聚合酶链式反应(qPCR)、IHC、ChIP和荧光素酶报告系统分析基因突变、DNA扩增和转录因子c-Myc在调节BCAT1表达中的作用。通过 RNA 干扰 (RNAi) 评估 BCAT1 在集落形成、细胞迁移和侵袭特性中的功能。正常上皮、低中度不典型增生组织、高度不典型增生组织和鼻咽癌组织中BCAT1蛋白表达阳性率分别为23.6%(17/72)、75%(18/24)、88.9%(8/9)和88.8%(71/80)。仅检测到外显子1中的1个SNP位点，42.4%（12/28）的鼻咽癌组织显示BCAT1中微卫星位点的扩增。 C-Myc可以直接与BCAT1启动子区的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53.6%（15/28）和59.1%（13/22）的鼻咽癌组织中共表达，并且BCAT1 mRNA表达在c-Myc敲低细胞系中也下调。此外，BCAT1 敲低细胞的增殖能力下降，细胞迁移和侵袭能力下降。我们的研究表明，基因扩增和c-Myc上调是原发性NPC中BCAT1过度表达的原因，并且BCAT1过度表达诱导细胞增殖、迁移和侵袭。结果表明BCAT1可能成为鼻咽癌诊断和治疗的新分子靶点。
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. 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). 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. 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.
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影响因子：
6.7
作者：
Kong QL;Hu LJ;Cao JY;Huang YJ;Xu LH;Liang Y;Xiong D;Guan S;Guo BH;Mai HQ;Chen QY;Zhang X;Li MZ;Shao JY;Qian CN;Xia YF;Song LB;Zeng YX;Zeng MS
通讯作者：
Zeng MS
影响因子：
2.5
作者：
Ben-Yosef, T;Eden, A;Benvenisty, N
通讯作者：
Benvenisty, N
DOI：
10.1164/ajrccm/142.6_pt_2.s27
发表时间：
1990-12-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
RODENHUIS, S;SLEBOS, RJC
通讯作者：
SLEBOS, RJC
影响因子：
4.8
作者：
Sun, Di;Zhang, Zhe;Hu, Lifu
通讯作者：
Hu, Lifu
DOI：
10.1016/s0167-4838(97)00044-7
发表时间：
1997-04-25
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY
影响因子：
--
作者：
Bledsoe, RK;Dawson, PA;Hutson, SM
通讯作者：
Hutson, SM