lncRNA通常被认为是非编码分子，通过表观方式调控下游基因。最新研究发现lncRNA也可在肿瘤中编码功能性小肽，而这常被以往研究所忽视。申请人前期工作发现lncRNA MIR155HG与肾透明细胞癌的发生发展呈正相关，且MIR155HG能够编码功能性小肽P155。该小肽能够靶向结合树突细胞（DCs）中的HSC70蛋白，且抑制其与伴侣分子HSP90的结合，而DCs介导的区域免疫对肾癌调控至关重要，我们据此假设: P155通过抑制HSC70-HSP90途径调节DCs的功能，进而调控肾透明细胞癌的区域免疫。本研究拟：1）通过CRISPR技术构建P155敲除或过表达的肾肿瘤细胞、类器官及小鼠模型，2）开展DCs功能检测及HSC70-HSP90分子网络阻断实验，明确P155-HSC70-HSP90分子网络对肾透明细胞癌及其区域免疫的调控作用及机制，项目的完成可能为肾癌区域免疫治疗提供新靶点。

lncRNA is generally considered to be a non-coding molecule that regulates downstream genes in an apparent manner. The latest research found that lncRNA can also encode functional small peptides in tumors, which is often ignored by previous studies. The applicant's previous work found that lncRNA MIR155HG is positively correlated with the occurrence and development of clear cell renal cell carcinoma(ccRCC), and MIR155HG can encode a functional small peptide P155. This small peptide can target the HSC70 protein in dendritic cells (DCs) and inhibit its binding to the chaperone molecule HSP90, and DCs-mediated regional immunity is essential for the regulation of kidney cancer. We hypothesized accordingly:P155 regulates the function of DCs by inhibiting HSC70-HSP90 pathway, which in turn regulates the regional immunity of ccRCC. This study intends to: 1) construct P155 knockout or overexpressed kidney tumor cells, organoids and mouse models by CRISPR technology, 2) carry out DCs function verification experiments and HSC70-HSP90 molecular network blocking experiments to clarify the regulation effect and mechanism of P155-HSC70-HSP90 molecular network on ccRCC and its regional immunity, the completion of the project can provide a new target for ccRCC regional immunotherapy.