我们前期验证HoxD10具有抑制胃癌生长和细胞增殖的重要功能 ，并能显著抑制胃癌细胞的侵袭。cDNA芯片及生物信息学分析提示肿瘤相关基因IGFBP3是HoxD10调控的重要候选靶基因，且IGFBP3启动子区域含HoxD10的结合序列。因此，我们推测HoxD10直接结合作用于IGFBP3启动子区，在转录水平调控其表达，从而影响胃癌细胞的侵袭能力。本研究将系统采用ChIP，EMSA和Luceferase分析等分子技术手段，验证HoxD10调控IGFBP3启动子的作用方式；基于外源性过表达和siRNA靶向干扰技术探讨HoxD10和IGFBP3对胃癌侵袭能力，上皮间质转化和细胞外基质降解的关键调控因子的作用；检测胃癌组织HoxD10和IGFBP3表达与肿瘤转移、临床预后的相关性。阐明HoxD10对IGFBP3的转录调控模式和对细胞侵袭的作用及机制，将为寻找新的胃癌靶标提供重要依据。

We have previously demonstrated that HoxD10 could inhibit gastric tumor growth, cell proliferation and invasion. cDNA microarray analysis and validation study showed that IGFBP3 was one of downstream target of HoxD10.In addition. Software prediction of transcription factor binding sites demonstrated that the promoter of IGFBP3 enriched with HoxD10 binding sites, so we hypothesis that HoxD1O could directly bind with special DNA sites and transcritionally regulate the expression of IGFBP3,thus affect the ablitiy of gastric cancer cell invasion. In this study, we will validate the potential DNA binding sites of IGFBP3 by HoxD10 by molucular technologic detection with ChIP, EMSA and luceferesa assays. Cell invasion and its related EMT and extracellular degradation biomarkers were determined in stable HoxD10 transfected gastric cancer cells with or withour siRNA knockdwon of IGFBP3. Morever, the expression level of IGFBP3 was detected in gastric cancer tissues and its clinical relevance with tumor metastesis and prognosis were analyzed. Unscoring the underlying mechanisms of the regulation of IGFBP3 by HoxD10 and its effect on cell invasion, will provide important evidence that searching potential biormarkers of gastric cancer.