Act1通过NF-κB和MAPKs信号通路促进结肠癌发生发展的机制研究

NF-κB (Nuclear factor-kappa B) and MAPKs (Mitogen-Activated Protein Kinases) signaling pathways play important role in various types of cancer development. Recent studies suggested that NF-κB activation factor 1 (Act1) can activate these signaling pathways, however, the role of Act1 in cancer remains elusive. Our prior preliminary work found that the expression of Act1 in human colorectal cancer (CRC) tissues increased significantly; Act1 promoted CRC cell lines colony formation, proliferation and migration. These findings suggested Act1 is likely to be a new oncogene, and promotes the development of CRC through the NF-κB and MAPKs signaling pathways. To prove the hypothesis, we will study the project as following: 1) we detect the expression level of Act1 in human patients specimens by RT-PCR and immunohistochemical analysis, and then analyze the association between the expression level of Act1 and human CRC patients clinicopathological parameters such as malignancy, metastasis and overall survival by statistical methods; 2) we determine the role of Act1 in CRC development by RNAi (RNA interfere) technology, colony formation assay, wound healing assay, tumor growth in nude mice model et al; 3) we check whether Act1 promotes the development of CRC through the NF-κB and MAPKs signaling pathways by the signaling pathway inhibitors and RNAi technology et al. The results of the project will shed light on the mechanism of Act1 in the development of CRC, and provide a new clue and promising target for the therapy of CRC.

NF-κB和MAPKs信号通路在多种肿瘤的发生发展中起重要作用，近期研究表明Act1（NF-κB 激活因子1）可以激活这些信号通路，但Act1在肿瘤中的作用仍不明确。本项目前期研究初步表明Act1在结肠癌组织中表达显著增高；并促进结肠癌细胞的克隆形成、增殖和迁移。上述研究提示Act1可能是一个新的致癌基因，通过NF-κB和MAPKs信号通路促进结肠癌的发生发展。为证实此假设，本项目拟：1）通过RT-PCR和免疫组化等技术检测Act1的表达水平，并分析其与结肠癌患者的恶性程度、转移、生存率等的相关性；2）采用RNA干扰、克隆形成、细胞划痕、裸鼠成瘤等技术研究Act1在结肠癌发生发展中的作用；3）应用信号通路抑制剂和RNA干扰等方法确定Act1 是否通过NF-κB和MAPKs信号通路促进结肠癌的发生发展。本项目的完成将初步阐明Act1在结肠癌发生发展中的作用机制，为其治疗提供新的线索和靶标。

NF-κB和MAPKs信号通路在多种肿瘤的发生发展中起重要作用，近期研究表明Act1（NF-κB 激活因子1）可以激活这些信号通路，但Act1在肿瘤中的作用仍不明确。本项目前期研究初步表明Act1在结肠癌组织中表达显著增高；并促进结肠癌细胞的克隆形成、增殖和迁移。上述研究提示Act1可能是一个新的致癌基因，通过NF-κB和MAPKs信号通路促进结肠癌的发生发展。为证实此假设，本项目拟：1）通过RT-PCR和免疫组化等技术检测Act1的表达水平，并分析其与结肠癌患者的恶性程度、转移、生存率等的相关性；2）采用RNA干扰、克隆形成、细胞划痕、裸鼠成瘤等技术研究Act1在结肠癌发生发展中的作用；3）应用信号通路抑制剂和RNA干扰等方法确定Act1 是否通过NF-κB和MAPKs信号通路促进结肠癌的发生发展。本项目的完成将初步阐明Act1在结肠癌发生发展中的作用机制，为其治疗提供新的线索和靶标。