LncRNA-uc001iot.1通过vimentin调控EMT诱导胰腺癌侵袭转移的作用及机制研究

Epithelial-mesenchymal transition (EMT) is the important mechanism of pancreatic cancer cell invasion and metastasis, while the role of EMT is always regulated by lncRNA, but the exact mechanism has not been clarified. Our previous study found that lncRNA-uc001iot.1 was overexpressed in pancreatic cancer, and silencing of lncRNA-uc001iot.1 inhibited pancreatic cancer cells invasive ability. In further we found that lncRNA-uc001iot.1 affected EMT protein marker E-cadherin expression,cell morphology and vimentin expression. Accordingly, we speculate that lncRNA-uc001iot.1 may regulate EMT through targeting vimentin signal pathway, and participate in pancreatic cancer invasion and metastasis. This project intends to detect the expression of lncRNA-uc001iot.1 and vimentin in pancreatic cancer, and further explore that there are some necessary correlations between them. To observe the changes of pancreatic cancer cell EMT conversion and invasion、metastasis, above pathways will be regulated in vivo and in vitro, and the expression in blood circulation level will be regularly detected. The implementation of this project will help further clarify the regulatory role and mechanism of lncRNA in EMT of pancreatic cancer cells, and provide new ideas for the early diagnosis and targeting treatment of pancreatic cancer.

上皮间质转化（EMT）是胰腺癌细胞发生侵袭转移的重要机制，同时EMT作用又受lncRNA的重要调控,但具体机制尚未阐明。我们前期研究发现胰腺癌高表达lncRNA-uc001iot.1，而lncRNA-uc001iot.1干扰后明显抑制其侵袭能力.进一步发现lncRNA-uc001iot.1影响EMT标记蛋白E-cadherin表达,细胞形态和vimentin表达。据此我们推测lncRNA-uc001iot.1可能通过靶向vimentin调控胰腺癌EMT过程，参与胰腺癌侵袭转移。本课题拟通过检测胰腺癌lncRNA-uc001iot.1与vimentin表达，探讨它们之间存在显著相关性；在体外和体内调控上述通路及血液循环水平上定期检测表达，研究胰腺癌细胞EMT和侵袭转移的改变。本项目的实施有助于深入理解lncRNA对胰腺癌细胞EMT的调控作用及分子机制，为其早期诊断和靶向治疗研究提供新思路。

上皮间质转化（EMT）是胰腺癌细胞发生侵袭转移的重要机制，同时EMT作用又受lncRNA的重要调控,但具体机制尚未阐明。本课题拟通过检测胰腺癌lncRNA-uc001iot.1与vimentin表达，探讨它们之间存在显著相关性；在体外和体内调控lncRNA-uc001iot.1/vimentin及血液循环水平上定期检测表达lncRNA-uc001iot.1，研究胰腺癌细胞EMT和侵袭转移的改变。我们研究发现胰腺癌高表达lncRNA-uc001iot.1，与胰腺癌患者的肿瘤大小，TNM分期，淋巴结侵袭和远处转移存在相关性。干扰lncRNA-uc001iot.1后明显抑制了胰腺癌细胞的增殖、EMT、侵袭迁移。通过靶点预测、蛋白质谱分析以及联合应用 lncRNA-uc001iot.1 及 vimentin 的 Knock-in 和 Knock-out 实验验证lncRNA-uc001iot.1通过vimentin发挥调控作用，进一步在裸鼠体内试验验证上述结果，通过患者术前、术后和转移复发过程患者血液lncRNA-uc001iot.1的表达，提示lncRNA-uc001iot.1可作为术后预测肿瘤复发的标记物，本项目的实施有助于深入理解lncRNA对胰腺癌细胞EMT的调控作用及分子机制，为其早期诊断和靶向治疗研究提供新思路.