nc886与核纤层蛋白laminA/C在前列腺癌侵袭转移中的作用及调控机制研究

项目名称： nc886与核纤层蛋白laminA/C在前列腺癌侵袭转移中的作用及调控机制研究

项目编号： No.81672834

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 孔璐

作者单位： 首都医科大学

项目金额： 25万元

中文摘要： 前列腺癌高度异质性是其区别于其它肿瘤的重要特点。最新研究提出laminA/C可能是肿瘤预后不良的标志物；新发现的非编码RNA886（nc886）甲基化失活亦是肿瘤预后不良的标志物。前期研究识别nc886在间质性质的人类宫颈癌及前列腺癌细胞系中高表达，然而在上皮性质的前列腺癌细胞系中低表达；前列腺癌细胞系中发现nc886可以结合laminA/C，它们在前列腺癌中的角色及具体调控机制，尚无文献报道。我们推测nc886和laminA/C可能是前列腺癌上皮间质转换过程中的重要标志物；nc886可能通过调控laminA/C改变核的稳定性。本项目拟从nc886在前列腺癌中的作用、调控及治疗三个层面揭示nc886与肿瘤预后的关联性、nc886与laminA/C及上皮间质转换信号通路的关联性及靶向前列腺癌中nc886的疗效及机制，为揭示新的肿瘤标志物及治疗靶标提供可靠的实验依据。

中文关键词： 非编码RNA；886；核纤层蛋白A/C；C14_前列腺肿瘤；侵袭与转移；标志物

英文摘要： The high inter-tumor heterogeneity of prostate cancer is an important feature that differents from the other tumors.The latest research suggests that lamin A/C may be a risk biomaker to estimate the prognosis of tumor; A novel type of non-coding RNA, nc886, in a wide variety of tumor may play the putative role of tumor suppressor, its deactivation by the method of the CpG methylation is a biomarker of poor prognosis in tumors. At the same time, nc886 is transcribed by RNA polymerase III (Pol III) and is the first case of a Pol III genes whose expression is regulated using the epigenetic silencing in several types of cancer. Here, our pilot study have identified that nc886 expression in human cervical cancer tissue, cell and prostate cancer cells with interstitial cell properties increased, however in the epithelium prostate cancer cells decreased; nc886 might bind laminA/C by reporter gene assay in prostate cancer cells; what role and the specific regulatory mechanism beween nc886 and laminA/C in prostate cancer have not been provided yet. We speculated that nc886 and laminA/C are putative important biomarkers in epithelial mesenchymal transition process of prostate cancer; In additon, nc886 may change the stable of the nuclear through regulating the laminA/C expression. We will investigate the role, the regulation mechanism beween nc886, laminA/C and some moleculars involving in the epithelial mesenchymal transition pathway, and the treatment by targeting nc886 in prostate cancer. Our project will focus on three aspect research to clarify the significance of abnormal expression of nc886 or laminA/C in prostate cancer progress. The first aim is to investigate the relevance between nc886, laminA/C and tumor prognosis; the second aim is to investigate the regulation mechanism and the emphasis on the relevance between nc886 and laminA/C and epithelial mesenchymal transition signal pathways; At last, our aim is to investigate the curative effect and mechanism when targeting nc886 in animal model of invasive prostate cancer. In summary, we will supply enough experimental datas to support our views for nc886 or laminA/C as a new molecular biomaker in the progression of prostate cancer and potentially novel target for invasive prostate cancer therapeutics.

英文关键词： non-coding RNA 886;laminA/C;prostate cancer; invasion and metastasis ;maker