去氧地胆草素通过解除linc00511对miR-370-5p核易位的阻滞重塑RNA激活效应抑制胰腺癌恶性生物学行为的机制研究

胰腺癌是世界范围内预后极差的消化道恶性肿瘤，严重威胁着人类健康，除手术外，积极有效的化疗能显著延长患者生存期，但不良反应及耐药性依然有待解决，开发新型抗肿瘤药物成为迫切需求。近些年，中医药为肿瘤治疗带来了一线希望，申请人前期研究发现，中药提取物去氧地胆草素具有显著抗胰腺肿瘤的作用并能改善化疗耐药，但具体机制仍不明确。鉴于此，本项目以胰腺癌为研究对象，采用多种细胞系、动物模型及大量病理标本通过生物信息学、分子生物学、实验动物学等实验方法，揭示去氧地胆草素抗胰腺肿瘤的具体机制，即通过解除linc00511对miR-370-5p核易位的阻滞，重塑RNA激活效应，上调p21表达，进而抑制胰腺癌恶性生物学行为。本项目的实施，旨在为改善胰腺癌预后提供新的用药方案，同时为中药提取物抗肿瘤研究提供新思路。此外，研究中发现的新型分子调控网络对于加深胰腺癌发病机理的认识也至关重要，并为胰腺癌诊疗提供新靶点。

Pancreatic cancer is a kind of gastrointestinal malignancy with poor prognosis worldwide which threatens human's health seriously. Effective chemotherapy can significantly prolong the survival of patients except operation. Due to the adverse drug reaction and chemoresistance, it is urgent to develop novel antitumor agents. In recent years, traditional Chinese medicine has provided a glimmer of hope for tumor therapy. In our previous study, it was verified that deoxyelephantopin, an extract derived from Chinese herbal medicine, possessed significant antitumor effect in pancreatic cancer and improved the chemosensitivity. However, the underlying mechanism remains unclear. In view of the above, pancreatic cancer is regarded as the research object and a variety of cell lines, animal models and a large number of pathological specimens are used to reveal the specific antitumor mechanism of deoxyelephantopin by applying bioinformatics, molecular biology and animal experiments. That is deoxyelephantopin inhibits the malignant biological behavior of pancreatic cancer by relieving the linc00511 mediated retardation on nuclear translocation of miR-370-5p, remodeling RNA activation and promoting p21 expression. The purpose of this study is to explore new strategy for improving the prognosis of pancreatic cancer, and to provide innovation for the antitumor research of traditional Chinese medicine extract. In addition, the novel molecular regulatory networks identified in present study are also meaningful to deeply understand the pathogenesis of pancreatic cancer and pinpoint new targets for diagnosis and treatment.