基于PDTX模型筛选的lncRNAs在胰腺癌化疗耐药调控网络中的作用及机制研究

化疗耐药是导致胰腺癌患者预后差的主要原因之一。目前研究表明，lncRNAs与肿瘤干细胞、EMT及肿瘤化疗耐药密切相关。因此，我们推测“lncRNAs-肿瘤干细胞-EMT-化疗耐药”形成复杂调控网络，而lncRNAs在该网络中发挥核心作用。本课题通过对耐药人源胰腺癌小鼠移植瘤模型（PDTX）进行高通量转录组测序，筛选出耐药相关的lncRNAs表达谱；通过系统生物信息学分析，精准高效挑选出耐药关键的lncRNAs，并构建耐药相关lncRNAs-靶基因调控网络。通过体外实验，研究lncRNAs对靶基因、胰腺癌干细胞、EMT和化疗敏感性的影响，明确lncRNAs的调控机制；通过动物实验，探索lncRNAs做为治疗靶点的潜在价值，并对胰腺癌患者手术标本进行检测，评估耐药相关lncRNAs做为患者预后判断指标的临床价值。经检索，国内外未见同类报道。

The chemoresistance is one of the main cause for poor prognosis in pancreatic cancer. According to recent studies, lncRNAs are closely related to tumor stem cells (CSCs), epithelial-mesenchymal transition (EMT) and chemoresistance. Therefore, we hypothesized lncRNAs-EMT-CSCs-chemoresistance formed a complex regulatory network, and lncRNAs play a critical role in this network. Our group will screen pivotal chemoresistance related lncRNAs by high-throughput sequencing and bioinformatics analysis system based on patient-derived pancreatic cancer xenograft models which are resistant to chemotherapy, and construct lncRNAs – targets regulatory network. We will further elucidate the function of screened lncRNAs in the modulation of targets, EMT, CSCs and chemosensitivity. At the same time, we plan to evaluate the potential value of lncRNAs as therapy targets by using xenograft mice models and as prognostic makers by detecting the resected specimens from pancreatic cancer patients. No similar research is reported.