非可控性炎症在肿瘤的发生发展中发挥重要作用。多炎性因子直接或间接激活下游NF-κB/STAT3信号通路是炎癌转化的重要步骤。集成课题组前期对炎症相关信号通路、表观遗传异常在多种癌症发生发展过程中的作用进行了大量研究。本项目将深入探索炎性因 (TNF-α,IL-1β等)激活的NF-κB/STAT3两个重要信号通路通过表观遗传调控影响肿瘤细胞恶性的分子(侧重miRNA与蛋白编码基因)，并确定其影响肿瘤细胞恶性表型的机制，并研究受该信号通路调控的分子是否也反馈调控这两个信号通路，从而阐明非可控性炎症持续存在促进肿瘤发生发展的新机制。同时在细胞和动物模型中探索外泌体介导的这类分子对肿瘤细胞的抗失巢凋亡及肿瘤前转移微环境形成的影响及机制，从而揭示非可控性炎症调控网络在肿瘤发生和转移中的作用及机制，并获得多炎性因子调控网络关键节点分子从而可能为炎症相关肿瘤的诊断和治疗提供新的靶点。

Nonresolving inflammation plays important roles in tumor initiation and progression. NF-κB/STAT3 signaling pathways activated by multiple inflammatory cytokines are driving factors for inflammation-related cancer. Our research groups have done plenty of research on the roles of inflammation-related signaling pathway and abnormal epigenetics in tumor initiation and development. In the present study, we will explore the role of the NF-κB/STAT3 signaling pathways activated by multiple inflammatory cytokines (mainly including TNF-α,IL-1β,IL-6,IL-17) in epigenetically regulating the malignant behavior of tumor cells and the potential mechanism. And further examine the existence of the positive feedback regulation between NF-κB/STAT3 signaling pathways and the genes regulated by the signaling pathways, which will clarify the novel mechanism that the persistent nonresolving inflammation promoting tumor initiation and development. Furthermore, we will investigate the mechanism by which the two signaling pathways regulating the tumor cell anoikis and the formation of pre-metastatic microenvironment. This study will fully reveal the role of the nonresolving inflammation in tumor initiation and progression and the specific mechanism underlying it. And the finding of the critical inflammatory network node molecules will provide new molecular targets for diagnosis and treatment of inflammation-related cancer.