LncRNA PVT1-YAP1/TEAD-miR1205轴调控食管腺癌进展的机制研究

食管腺癌具有与食管鳞癌不同的分子遗传学特征和发病机制。申请人在前期研究中发现了miR-1205在食管腺癌中显著高表达，且与不良预后密切相关。结合生物信息学的结果，提示miR-1205的转录可能受YAP1/TEAD转录复合物的调控。申请人已发表的成果证明，PVT1-YAP1轴是促进食管腺癌进展的重要分子机制。miR-1205在食管腺癌中相关功能的发现，则进一步完整了PVT1-YAP1轴的通路链条。因此，本项目原创性地提出了PVT1-YAP1/TEAD-miR-1205轴调控食管腺癌进展的科学假设，并已筛选出miR-1205的候选靶基因。本项目将在前期工作的基础上，①进一步阐明miR-1205在食管腺癌中的临床意义及生物学功能；②明确YAP1/TEAD调控miR-1205转录的分子机制；③揭示miR-1205下游的靶基因及其在食管腺癌中的生物学功能。

Esophageal cancer is the sixth most common cause of cancer-related death worldwide. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated esophageal squamous cell carcinomas (ESCC) from esophageal adenocarcinomas (EAC). Our recent preliminary data demonstrated that miR-1205 expression was up-regulated in EAC, and high expression of miR-1205 was associated with poor survival. According to bioinformatic analysis, YAP1/TEAD complex is likely to be the transcription factor of miR-1205. The published results of the applicant have demonstrated that the PVT1-YAP1 axis play a role in promoting the progression of EAC. To uncover miR-1205's function in EAC will further completes the pathway of the PVT1-YAP1 axis. Therefore, the scientific hypothesis of PVT1-YAP1/TEAD-miR-1205 axis to regulate the progression of EAC is proposed in this project. Furthermore, we initially screened out the candidate target genes of miR-1205(SH3BP2 and others). Based on the previous work, the project will ①further clarification of the clinical significance and biological function of miR-1205 in EAC; ②Clarify the molecular mechanism of YAP1/TEAD regulation miR-1205 transcription; ③Uncovering the target genes downstream of miR-1205 and their biological functions. The completion of this project will provide an important theoretical basis for revealing the molecular mechanisms associated with the progression of esophageal adenocarcinoma.