circRNA0007766/miR4492/MET/PI3K-Akt通路调控食管胃结合部腺癌增殖和侵袭的分子机制研究

环状RNA在肿瘤发生、发展中发挥着重要的生物学功能。我们前期通过RNA-seq、生物信息学分析、细胞实验筛选出circRNA0007766为调控食管胃结合部腺癌（AEG）增殖、侵袭能力的关键环状RNA，并推断其可能通过阻遏miR4492/Ago2形成的RNA沉默诱导复合体对MET mRNA降解，从而调控肿瘤细胞的恶性表型。本课题拟在AEG组织和血浆中检测circRNA0007766、miR4492和MET的表达及与临床病理预后的关系；探索circRNA0007766通过“分子海绵”作用阻遏miR4492/Ago2对MET mRNA降解的机制以及MET是否可激活其下游PI3K-Akt蛋白信号通路影响AEG恶性表型。本研究课题旨在阐明circRNA0007766通过miR4492/MET/PI3K-Akt通路促进AEG增殖和侵袭能力的分子机制，为食管胃结合部腺癌的临床诊断及治疗提供新的靶点。

Circular RNA recently was reported to play an important role in tumorigenesis. Our preliminary study identified that circRNA0007766 was a key circular RNA in promoting cellular proliferation and invasion of adenocarcinoma of the esophagogastric junction (AEG) with RNA-seq, bioinformatics analysis and tumor proliferation/invasion assays. We hypothesize that circRNA0007766 might regulate malignant biological behavior of AEG via miR4492/MET signaling pathway. In this study, we propose to evaluate the expression level of circRNA0007766, miR4492 and MET in primary AEG tissues and blood samples from patients, and further explore their correlation with clinicopathological characteristics and prognosis. In addition, we will investigate the molecule mechanism by which circRNA0007766 inhibits miR4492/Ago2 complex leading to MET down-regulation, clarifying whether MET expression level and activation impact AEG cell proliferation and invasion through PI3K-Akt signaling pathway. This research project will provide a better understanding of the molecular mechanism of circRNA0007766 in the progression of AEG and shed a new light for designing novel treatment strategies for AEG.