膀胱肿瘤细胞外泌体circRNA_0013936促进PMN-MDSCs分化并上调FATP2和下调RIPK3介导免疫逃逸的机制研究。

多核型髓源性抑制细胞（PMN-MDSCs）是肿瘤微环境中重要的抑制性免疫细胞。在前期研究中，我们发现：肿瘤微环境中存在大量的PMN-MDSCs，且FATP2表达上调，RIPK3表达下调。目前，导致该现象的分子机制尚不清楚。我们通过预实验和高通量测序发现：膀胱肿瘤细胞外泌体中具有分子海绵作用的circRNA_0013936可能是介导上述现象的关键分子。我们推测：膀胱肿瘤细胞可能是通过外泌体circRNA_0013936调控miRNA-320a和miRNA-301b，启动相关信号通路，促进PMN-MDSCs分化并上调FATP2和下调RIPK3，进而介导肿瘤的免疫逃逸。本课题拟通过一系列细胞实验和动物实验，阐明膀胱肿瘤细胞通过外泌体circRNA_0013936促进PMN-MDSCs分化并上调FATP2和下调RIPK3介导免疫逃逸的新机制，为膀胱肿瘤的防治提供新的思路。

Multinuclear myeloid-derived suppressor cells (PMN-MDSCs) is an important suppressor immune cell in the tumor microenvironment. In our previous study, we found that the bladder tumor tissue was infiltrated with a large number of PMN-MDSCs. Moreover, the FATP2 expression was up-regulated, and the RIPK3 expression was down-regulated. At present, the molecular mechanism leading to this phenomenon is unclear. Through pre-experiment and sequencing technology, we found that circRNA_0013936, which has a molecular sponge effect in the bladder tumor cell-derived exosomes, may be a key molecule that mediates the above phenomenon. We speculate that bladder tumor cell-derived exosomal circRNA_0013936 may promote PMN-MDSCs differentiation, up-regulate FATP2 and down-regulate RIPK3 by regulating miRNA-320a and miRNA-301b and activating related signaling pathways, thereby mediating tumor immune escape. This study will perform a series of cell and animal experiments to elucidate a new mechanism by which bladder tumor cell-derived exosomal circRNA_0013936 mediates immune escape by promoting PMN-MDSCs differentiation, up-regulating FATP2 and down-regulating RIPK3. This study will provide new ideas for the prevention and treatment of bladder cancer.