miR-223促进胰腺癌恶性生物学行为的分子机制及临床意义研究

项目名称： miR-223促进胰腺癌恶性生物学行为的分子机制及临床意义研究

项目编号： No.81502126

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 马佳

作者单位： 蚌埠医学院

项目金额： 18万元

中文摘要： 胰腺癌是一种常见的恶性消化道肿瘤，近年来发病率及死亡率在全球呈现逐渐上升的趋势。因此加强胰腺癌的基础与临床研究意义重大。近年来，miRNA作为肿瘤治疗靶点的研究有重要进展，部分miRNA类药物已进入临床实验阶段。我们前期发现：miR-223促进胰腺癌细胞增殖、迁移及侵袭，发挥癌基因功能；胰腺癌细胞对吉西他滨产生耐药与miR-223表达增加并导致EMT发生有关，提示miR-223可能是胰腺癌的潜在治疗靶点。结合预实验，本课题拟围绕miR-223这一靶点，首先探讨SP1转录调控miR-223和miR-223调控PDS5B并进而促进胰腺癌恶性生物学行为的分子机制；其次探讨miR-223在胰腺癌组织中的表达及临床意义，及miR-223抑制剂加强化疗药物吉西他滨对胰腺癌疗效的作用及机制，以初步评价miR-223作为胰腺癌新的分子靶标的临床应用价值，从而为日后向临床应用转化提供理论和实验依据。

中文关键词： 胰腺外分泌肿瘤；miR-223；PDS5粘连蛋白相关因子B；SP1

英文摘要： Pancreatic cancer (PC) is one of the common malignant tumors of digestive tract. Since incidence and mortality rates of PC are increased in the recent years in worldwide, it is pivotal to investigate the basic and clinical study in PC. Recently, the role of microRNAs as the therapeutic targets has been achieved an important progress and some of miRNAs are in clinical trial. Our previous study has demonstrated that miR-223 promotes PC cell growth, migration, and invasion, suggesting an oncogenic role of miR-223 in PC. Moreover, miR-223 is critically involved in gemcitabine resistant-triggered EMT in PC cells, indicating that miR-223 could be a potential target for the treatment of PC. Therefore, based on our preliminary results, we will further determine the role of miR-223 in the PC progression and drug resistance. Firstly, we will define whether SP1 regulates miR-223 and miR-223 controls PDS5B, leading to governing PC malignant biological behavior. Secondly, we will detect the relationship between expression of miR-223 and clinic pathological features of PC patients and dissect whether miR-223 inhibitors enhance the sensitivity of gemcitabine in PC patients. Our study will provide the insight onto evaluation of miR-223 as a new molecular target and obtain theoretical and experimental basis for using miR-223 inhibitors in clinical in the future.

英文关键词： pancreatic cancer;miR-223;PDS5B;SP1