在结直肠癌患者体内，Th17细胞的炎症及免疫调节作用对肿瘤的发生发展作用关键，但初始CD4+T细胞向Th17细胞分化分子机制尚不清楚。本课题前期研究显示，结直肠癌患者外周血和肿瘤组织CD4+T细胞中，长链非编码RNA NEAT1表达显著升高，干扰其表达可抑制CD4+T内RORγt表达和IL-7分泌，抑制初始CD4+T向Th17分化；此外发现NEAT1与CD4+T内miR-93及STAT3表达关系密切，并受NF-κB正调控。我们由此推测，直肠癌CD4+T细胞通过NF-κB使NEAT1高表达，抑制miR-93表达及活性，影响其向Th17分化，影响结直肠癌发生发展。该项目旨在分子、细胞和模式动物水平上，借助各种分子生物学手段，研究NEAT1调控Th17分化及其在结直肠癌发生发展中的作用。本项目的完成不仅有助于阐明NEAT1在结直肠癌Th17细胞分化中的内在机制，也为直肠癌防治提供理论基础。

In colorectal cancer (CRC), It is well known that inflammation and immune regulation of Th17 cell plays an important role in CRC occurrence and development. However, the molecular mechanism of Th17 cell differentiation from naïve CD4+T in CRC is unclear. Our preliminary results showed that lncRNA-NEAT1 expression was significantly increased in peripheral blood CD4+T cells and tumor infiltrating CD4+T cells from CRC patients. Downregulation of NEAT1 in CD4+T cells could decrease RORγt expression and IL-17 secretion. Inhibition of NEAT1 in naïve CD4+T reduced Th17 cell differentiation. In addition, NEAT1 in CD4+T cell were closely related to the expression of miR-93 and STAT3, and which is positive regulated by NF-κB. As a result, we speculated that activation of NF-κB contributed to the increase of NEAT1 expression, resulting in the decrease of miR-93 expression, which are essential for Th17 cell differentiation. In this study, we aim to demonstrate the effect of NEAT1 on differentiation of Th17 cell in CRC occurrence and development using a series of in vivo and in vitro technology. We will further explore the molecular mechanism of NEAT1 on Th17 cell differentiation in CRC, trying to provide theorey for prevention and treatment of colorectal cancer.