STOML2在炎症恶性转化中的机制研究

炎症与肿瘤等复杂疾病的发生发展关系密切，已有证据表明慢性炎症是部分肿瘤发生的决定因素之一，阐明炎症诱发肿瘤的机制以及有效预警和高效干预该进程，已成为肿瘤生物学领域的前沿热点。我们前期对肿瘤相关的炎性调控机制进行了初步探索（Oncogene, 2012; JBC, 2010），近期通过文库筛选又发现，干涉STOML2基因可显著抑制TNFa激活的NF-kB通路活性。与癌旁组织相比，STOML2表达水平在人结肠炎相关结肠癌样本中显著上调，提示STOML2炎性相关肿瘤的发生发展过程中发挥重要作用，而相关机制仍有待阐明。本项目将利用现有的分子和细胞模型，结合AOM/DSS结肠炎相关结肠癌和原位结肠癌动物模型，分析STOML2对炎性恶变过程的影响及相关调控机制，并计划通过临床样本评价STOML2表达水平与结肠炎相关结肠癌发生发展和预后的相关性，为阐明炎性相关肿瘤的发生机制和防治提供新的思路和实验基础。

Inflammation conditions, generally caused by genetic mutations, autoimmune diseases, and exposure to environmental factors can increase the risk of cancer. Inflammatory responses play decisive roles at different stages of tumor development, including initiation, promotion, malignant conversion, invasion, and metastasis, but the mechanisms involved are most elusive. Our previous studies have been focused on the regulatory mechanism of cancer-related inflammation and functional analysis of key regulatory proteins (Oncogene, 2012; JBC 2010), and our recent data showed that knockdown the expression of STOML2 could significantly inhibit the activity of NF-kB induced by TNFa. More importantly, we found that the expression level of STOML2 was much higher in colitis associated cancer (CAC) specimens compared with the adjacent areas. These data suggested that STOML2 may play critical roles in the process of inflammation-related tumorigenesis. In this proposal, we will try to demonstrate whether or how STOML2 is involved in the regulation of inflammation, further we will analyze the relationship between STOML2 expression level and the grade of CAC with a large number of clinical samples. This study might expand our comprehensive understanding of the complex incentives and regulatory mechanisms of inflammation-related tumorigenesis, and also might provide a theoretical basis for potential drug targets and early diagnostic markers to prevent or interfere with this process.