HOXC6 Is Deregulated in Human Head and Neck Squamous Cell Carcinoma and Modulates Bcl-2 Expression
HOXC6 Is Deregulated in Human Head and Neck Squamous Cell Carcinoma and Modulates Bcl-2 Expression
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DOI：
10.1074/jbc.m112.361675
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发表时间：
2012-10-12
影响因子：
4.8
通讯作者：
Ahn, Sang-Gun
中科院分区：
文献类型：
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作者：
Moon, Sung-Min;Kim, Soo-A;Ahn, Sang-Gun
同源异型盒C6（HOXC 6）基因属于同源异型蛋白转录因子家族，在胚胎发育的形态发生和细胞分化中起重要作用。本研究旨在探讨HOXC 6在人头颈部鳞状细胞癌（HNSCC）中对Bcl-2的调控作用。HOXC 6和Bcl-2基因被鉴定为在HNSCC组织和细胞系中过表达。转染实验表明HOXC 6能增加Bcl-2 mRNA和蛋白的表达。荧光素酶报告基因分析表明HOXC 6诱导了Bcl-2启动子的活性。检测了一系列Bcl-2启动子缺失突变体，并鉴定出最小的HOXC 6响应区位于Bcl-2启动子的TAAT基序（~ 420 bp）中。有趣的是，使用siRNA抑制HOXC 6导致Bcl-2表达的抑制和诱导caspase-3依赖性凋亡; HNSCC细胞中HOXC 6的过表达增加了对紫杉醇诱导的凋亡的抵抗。总之，我们的研究结果表明，HOXC 6是通过调节Bcl-2表达的抗凋亡途径的重要机制。
Homeobox C6 (HOXC6) genes belong to the homeoprotein family of transcription factors, which play an important role in morphogenesis and cellular differentiation during embryonic development. The aim of this study was to explore the role of HOXC6 in the regulation of Bcl-2 in human head and neck squamous cell carcinoma (HNSCC). The HOXC6 and Bcl-2 gene were identified as being overexpressed in HNSCC tissue and cell lines. Transfection assays demonstrated that HOXC6 increased the levels of Bcl-2 mRNA and protein. A luciferase reporter assay suggested that HOXC6 induced activity of the Bcl-2 promoter. A series of Bcl-2 promoter deletion mutants were examined and the minimal HOXC6-responsive region was identified to be in the TAAT motif (-420 bp) of the Bcl-2 promoter. Interestingly, the inhibition of HOXC6 using siRNA led to the repression of Bcl-2 expression and induced caspase-3-dependent apoptosis; overexpression of HOXC6 in HNSCC cells increased the resistance to paclitaxel-induced apoptosis. Together, our findings suggest that HOXC6 is an important mechanism of the anti-apoptotic pathway via regulation of Bcl-2 expression.