HOXB7基因促胃癌转移机制研究

Our preliminary study（Gene Arry Screen） has recognized that HOXB7 is a important gene in gastric cancer metastasis. HOXB7 is over-expression in gastric cancer and decrease its expression in gastric cancer cell can significantly inhibit the proliferation, migration and invasion of gastric cancer cells,and also can up-regulate Vimentin, down-regulate E-Cadherin expression.But the functional significance of HOXB7 gene in gastric cancer and its mechanism of promoting metastasis is remain need to explore in this project.In this project, the stable expression of HOXB7 and RNA interferenced cells are used as a cell model.Using the Trans-well, cell cloning, Gene arry screen,siRNA interference, signal path blocking and histopathologic IHC experiments,to study the effect of HOXB7 gene on gastric cancer invasion and migration ability both in vitro and in vivo. And to research the molecular mechanism and related signaling pathways involved in the downstream,such as ERK pathway in HOXB7 promote gastic cancer metastasis from EMT,blood vessels and lymphatic vessel formation.Those reseach to provide a strong scientific basis for application the HOXB7 as potential new targets of stomach cancer treatment.

我们前期通过基因芯片筛选出一个与胃癌发生及转移密切相关的基因---HOXB7。预实验证明其HOXB7在胃癌组织中表达上调；抑制HOXB7表达能够抑制胃癌细胞增殖、克隆形成、侵袭迁移能力，同时上调Vimentin、下调E-Cadherin表达。但其在胃癌中的功能意义以及促转移作用及分子机制仍有待深入探讨。本项目拟通过一系列细胞实验、动物实验、基因芯片、siRNA干扰、信号通路阻断以及病理组织IHC等实验，研究HOXB7在胃癌中的生物学作用及其促胃癌EMT、血管淋巴管形成的相关下游分子机制和参与其中的相关信号通路，阐明ERK通路在HOXB7促血管和淋巴管形成、EMT现象和侵袭迁移之间的调控作用。体内外实验研究HOXB7促胃癌转移的分子机制，为应用以HOXB7作为胃癌治疗的潜在新靶点，提供有力的科学依据。

本项目通过PCR、IHC及WB等实验手段证明HOXB7在胃癌组织中表达上调，其上调与胃癌的病理分期、淋巴结转移、血管密度及预后有关；同时体内外实验表明，抑制HOXB7表达能够抑制胃癌细胞增殖、克隆形成、侵袭迁 移能力，同时上调E-Cadherin和下调Vimentin表达及血管淋巴管形成；同时过表达HOXB7的表达能够显著促进胃癌的增殖侵袭转移及EMT能力。进一步利用基因芯片、蛋白芯片及MAPK通路小分子的抑制剂及免疫荧光等实验，发现MAKP通路中的P38、ERK、AKT通路参与HOXB7促血管和淋巴管形成、EMT现象和侵袭迁移的调控作用。通过本项目的研究，为应用以HOXB7作为胃癌治疗的潜在新靶点，提供有力的科学依据。