肿瘤微囊泡中microRNA-23a调节树突状细胞分化的作用机制

The production of microvesicles(MV) by tumor cells has been implicated in tumor associated immune suppression. We demonstrate that microvesicle by produce CT26 tumor cells inhibited the differentiation of myeloid dendritic cells (DC), promote DC cells apoptosis and reduce the absolute number cells. As a result, it damaged antigen uptake, antigen presented and secretion IL-12p70 of DC. MicroRNA (miRNA) chip found that miRNA-23a expression significantly improved in the MV; and DC phenotypic was changed after transfected miRNA-23a. Therefore, we inferred that miRNA-23a may regulate the DC cell differentiation and function without others reported. This study will reveal the mechanism miRNA-23a in tumor MV regulate DC cell function by integrating miRNA microarray, bioinformatics analysis, luciferase reporter gene and RNA interference research tools. These data will suggest that miRNA-23a in tumor MV regulate DC cell differentiation and function; and provide new ideas and choices for further investigate the mechanism, diagnosis and treatment of the tumor.

肿瘤分泌的微囊泡(Microvesicle, MV)在肿瘤微环境中起重要作用，MV可以降低免疫细胞活性，促进免疫耐受，发挥免疫抑制功能。本课题前期研究发现小鼠结直肠癌细胞分泌MV抑制髓系树突状细胞分化，促进DC细胞凋亡，降低DC细胞抗原摄取、递呈能力、IL-12p70分泌减少；miRNA芯片发现miRNA-23a在MV中明显富集，表达miRNA-23a慢病毒感染DC发现DC细胞表型改变，由此推测miRNA-23a可能调控髓系DC细胞分化，目前未见miRNA-23a调节DC功能的报道。本研究采用miRNA芯片、生物信息学分析、荧光素酶报告基因和RNAi干扰等研究手段，对肿瘤MV中miRNA-23a调节DC细胞功能及其靶基因进行研究，揭示其作用机制；丰富肿瘤MV中miRNA对DC细胞分化调控的理论，为探讨肿瘤发生机制及治疗提供新思路。