SOX4调控IL-6/NF-κB信号通路促进口腔扁平苔癣癌变的作用及机制研究

Oral lichen planus(OLP) is a kind of oral mucosal T cells mediated bynoninfectious chronic inflammation of oral mucosal diseases, is a common disease. Despite it was listed by WHO as precancerous lesions, the mechanism of oral lichen planus carcinogenesis was not clear. Our research group firstly found SOX4 protein form OLP related oral squamous cell carcinoma tissue, but the relationship between SOX4 and OLP, so far there is no report. We also found that SOX4 was high expressed in OLP related oral squamous cell carcinoma cells, and low expression in normal human oral keratinocytes cells，and OLP related oral squamous cell carcinoma cells proliferation decreased after knocking down SOX4 gene in our previous studies. IL-6 plays an important role in occurrence and development of OLP as a mediator ofinflammation. We hypothesized that SOX4 may promote OLP carcinogenesis via the signaling pathway by IL-6 mediated. To confirm this hypothesis, we establish OLP cell model in vitro and study the growth changes of OLP related oral squamous cell carcinoma cell in vitro and in vivo after knocking down SOX4 gene. We will study the mechanism of SOX4 in the process of OLP carcinogenesi through NF- κB signal pathway, so as to preliminary clearly clarify the relationship between carcinogenesis of OLP and the expression of SOX4. The results will provide a new idea and index for the further study of the relationship between the mechanism chronic inflammation with OLP as a model of the microenvironment and tumor.

口腔扁平苔藓（oral lichen planus, OLP）是一种T细胞介导的口腔黏膜慢性非感染性炎症，被WHO列为癌前病变，但其具体癌变机制不明确。本课题组首次发现SOX4蛋白高表达于OLP相关的人类口腔鳞状细胞癌组织，但SOX4与OLP癌变的关系国内外目前尚无报道。我们前期研究发现SOX4在来源于OLP的人口腔鳞癌细胞中高表达，在正常人口腔角质上皮细胞中低表达；SOX4基因沉默后，OLP相关的口腔鳞癌细胞增殖能力降低。IL-6作为一种炎症介质，在OLP的发生发展中起着重要的作用。我们推测SOX4可能通过IL-6的介导作用于肿瘤信号通路而促进OLP癌变的发生。我们拟通过建立体外OLP细胞模型，研究SOX4对来源于OLP的人口腔鳞癌细胞体内外生长变化的影响,并以NF-κB通路为切入点，探索SOX4对于IL-6介导的NF-κB通路的调控作用，揭示口腔黏膜慢性炎症转化为口腔鳞癌的内在机制。

口腔鳞状细胞癌（oral squamous cell carcinoma, OSCC）是人头颈部最常见的恶性肿瘤之一，占全身肿瘤的 3%。每年全球有 50万新发病例，而其中只有 50%的患者生存率大于 5 年。由于 OSCC 的发生机制仍未明确，临床仍很难把握其发生、发展和预后。口腔扁平苔藓（oral lichen planus, OLP）是一种T细胞介导的口腔黏膜慢性非感染性炎症，被WHO列为癌前病变，但其具体癌变机制不明确。本课题组首次发现SOX4蛋白高表达于OLP 相关的人类口腔鳞状细胞癌组织，但SOX4与OLP癌变的关系国内外目前尚无报道。课题组经过一系列研究发现SOX4在来源于OLP的人口腔鳞癌细胞中和单纯口腔鳞癌中均高表达，在正常人口腔角质上皮细胞中低表达；SOX4基因沉默后，口腔鳞癌细胞增殖能力，迁移能力和侵袭能力均明显降低。在炎症相关肿瘤启动子NF-κB信号通路的研究中证实SOX4促进了NF-κB的转录活性。IL-6作为一种炎症介质，在OLP的发生发展中起着重要的作用。我们继续探索SOX4对于IL-6介导的NF-κB通路的调控作用，以NF-κB通路为切入点，通过流式细胞术，荧光素酶报告基因活性实验等证明了SOX4能促进IL-6介导的NF-κB信号通路的激活，上述结果证实我们的假说即SOX4可能通过某种细胞因子的介导作用于NF-κB信号通路而促进口腔扁平苔藓相关的人口腔鳞癌细胞的增殖发展。