长链非编码RNA（lncRNA）在肿瘤发生发展中发挥重要的作用，阐明其异常调控的分子机制具有重要意义。食管鳞癌是中国的特色肿瘤，目前缺乏诊断的特异标志物以及靶向治疗的分子靶点。我们在前期研究中发现：①食管鳞癌组织在染色体3q23-25处有多个lncRNA存在特异性的基因扩增，其中PISRT1表达上调最为明显；②PISRT1与Parkin蛋白RING0结构域特异性地结合而促进了Parkin泛素连接酶活性；③同时，PISRT1可通过ceRNA调控线粒体自噬相关蛋白的表达；从而PISRT1多层面诱导线粒体自噬，进而增强食管鳞癌细胞的干细胞样特性，并促进其肿瘤生长及转移。本项目将根据前期研究结果，综合采用分子生物学、细胞生物学并结合模式动物等研究手段，深入探讨PISRT1调控线粒体自噬促进其肿瘤生长及转移的详细分子机制，为lncRNA调控肿瘤转移提供新的理论依据以及食管鳞癌的临床诊治提供新的靶标。

Long non-coding RNA (lncRNA) plays an important role in tumor development and progression. It is of great significance to elucidate the biological role and molecular mechanism of deregulated lncRNA in cancer. Esophageal squamous cell carcinoma is most prevalent in china, where more than half of the new incidences worldwide happen. However, there is no effective diagnosis marker and therapeutic target. Recently, we found that lncRNA-PISRT1 was specifically amplified and overexpressed in ESCC samples. We then found that PISRT1 bound the RING0 domain of Parkin protein to stimulate its E3 ligase activity in ubiquitination. Meanwhile, PISRT1 can also act as ceRNA to inhibit multiple miRNA, leading to upregulation of mitophagy-associated genes. Thus, these results indicate that PISRT1 promotes mitophagy via different mechanisms. Furthermore, we demonstrate that PISRT1 enhances stem-like phenotypes and metastasis via mitophagy. In this project, we aim to explore the biological roles and underlying mechanisms in which PISRT1 promotes mitophagy and metastasis, which might provide new biomarkers and potential targets for diagnosis and therapy of esophageal cancer.