溶酶体在抗感染免疫过程中有重要作用，但其调控机理还有待于进一步研究。申请人通过miRNA-mRNA共测序分析发现，牙鲆感染海豚链球菌后，miR-7133和PC-3p-9227显著低表达，且均靶标于溶酶体膜蛋白基因lamp2，它们与lamp2之间是负调控关系，这两个miRNAs在调控溶酶体参与的免疫应答中有潜在的重要作用。基于前期的研究结果，本项目将继续聚焦于miR-7133、PC-3p-9227和lamp2的功能与调控机制，阐明它们的时空表达特征和调控模式；进一步利用RNA干扰、基因过量表达等技术，通过体内、体外实验明确miR-7133和PC-3p-9227及lamp2在牙鲆抗海豚链球菌侵染中的作用，同时进一步解析miRNA调控溶酶体参与的免疫应答。研究结果将加深我们对鱼类miRNA作用机制的理解，同时为海豚链球菌病的防控提供理论参考。

Lysosomes play important roles in the regulation of host immune response, however, the mechanisms need to be further studied. We had performed the miRNA-mRNA co-sequencing in Japanese flounder challenged by Streptococcus iniae and found that the expressions of miR-7133 and PC-3p-9227, were significantly decreased compared to the health group, both of the miRNAs target to the lamp2 (lysosome membrane protein 2) gene in Japanese flounder, and there is a negative regulation relationship between the miRNAs and lamp2. The two miRNAs play a potentially important role in regulating the immune response involved by lysosomes. Based on these preliminary results, we will pursue the function and mechanism of lamp2 regulated by miR-7133 and PC-3p-9227 in Japanese flounder, clarify their temporal and spatial expression patterns, study the effects of miR-7133, PC-3p-9227 and lamp2 on Japanese flounder responding to Streptococcus iniae infection via in vivo and vitro experiments by using methods including overexpression and RNAi, and further explore the mechanism of miRNA regulating the immune response involved by lysosomes. Our results will deepen our understanding of the regulated mechanism of miRNA in fish and provide guidance for the prevention and control of Streptococcus iniae diseases.