Department of Pathology, College of Dentistry, Chosun University, Gwangju, 501-759.
Department of Biochemistry, Oriental Medicine, Dongguk University, Gyeongju, 780-714, Republic of Korea.
J Biol Chem. 2012 Oct 12;287(42):35678-35688. doi: 10.1074/jbc.M112.361675. Epub 2012 Aug 15.
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.
同源盒 C6 (HOXC6) 基因属于转录因子的同源蛋白家族，在胚胎发育过程中对于形态发生和细胞分化起着重要作用。本研究旨在探讨 HOXC6 在调控人头颈鳞状细胞癌 (HNSCC) 中的 Bcl-2 中的作用。HOXC6 和 Bcl-2 基因在 HNSCC 组织和细胞系中被鉴定为过度表达。转染实验表明 HOXC6 增加了 Bcl-2 mRNA 和蛋白的水平。荧光素酶报告基因检测表明 HOXC6 诱导了 Bcl-2 启动子的活性。对一系列 Bcl-2 启动子缺失突变体进行了检测，鉴定出 HOXC6 反应的最小区域位于 Bcl-2 启动子的 TAAT 基序 (-420 bp)。有趣的是，使用 siRNA 抑制 HOXC6 导致 Bcl-2 表达的抑制，并诱导 caspase-3 依赖性凋亡；HOXC6 在 HNSCC 细胞中的过表达增加了对紫杉醇诱导凋亡的抗性。总之，我们的研究结果表明 HOXC6 是通过调节 Bcl-2 表达来抑制细胞凋亡途径的重要机制。
