平滑肌（SM）22是新近发现的一种与细胞转化和肿瘤不良预后有关的细胞骨架相关蛋白，具有抗炎和抗增殖活性。在肿瘤和转化的细胞中，SM22表达下调。我们假设，SM22缺失介导的NF-κB活化是大肠癌慢性炎症新的信号调节机制。本项目拟探讨临床大肠癌组织SM22下调与肿瘤炎症标志物表达活性的关系及其与大肠癌进展的临床病理相关性；分析大肠癌组织的sm22启动子甲基化水平、TGFβ-Smad3途径活性和SM22泛素化降解速率，在细胞水平上，分别从表观遗传学、信号转导和蛋白质修饰角度，阐明大肠癌SM22表达缺失的分子机制；通过考察SM22对大肠癌细胞IκBα-NF-κB、CK-II- NF-κB和Sirt1- NF-κB相互作用的影响，揭示SM22缺失激活NF-κB的信号途径和干预靶点。利用sm-/-小鼠建立大肠癌模型，证实体内SM22的抗炎和抗肿瘤活性。以期为大肠癌炎症学说提供新的理论依据及药物靶标。

Smooth muscle (SM) 22 (namely transgelin) is recently identified as a novel biomarker which is closely associated with poor prognosis in colorectal cancer patients. SM22 inhibits inflammation and cell proliferation. The disruption of SM22 has been reported in a variety of cell types on transformation. We hypothesized that the disruption of SM22 may be the novel molecular mechanisms which results in the development and poor prognosis in colorectal cancer via activation of NF-κB pathway. To address this issue, we will identify the characteristics of SM22 expression and investigate the relationship among downregulation of SM22, NF-κB activation and inflammatory factor expression in patients with colorectal cancer. The project is going to determine the mechanisms of SM22 disruption in colorectal cancer based on the perspective of epigenetics, signaling transduction and protein modification, respectively, and to clarify the signaling pathways of SM22 disruption activating NF-κB, as well as the relationship with tumor cell growth and invasion. The project will confirm the antiinflammation and antineoplasmic activity of SM22 in vivo using colorectal cancer model in Sm22?/? mice. Our research will find new molecular therapeutic target, provide insight for understanding the molecular mechanisms governing colorectal cancer development as well as predicting the prognosis of colorectal cancer patients.