长链非编码RNA PCAT-1在前列腺癌细胞中的功能机制研究

项目名称： 长链非编码RNA PCAT-1在前列腺癌细胞中的功能机制研究

项目编号： No.31501037

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 陈伟

作者单位： 中国科学院微生物研究所

项目金额： 20万元

中文摘要： 长链非编码RNA在癌症的发生、发展及转移中发挥着重要功能，对于癌症早期诊断和治疗有着重要的应用价值。长链非编码RNA PCAT-1在恶性前列腺癌细胞中高表达，通过调控c-myc、brca2等基因促进前列腺癌细胞的增殖，但其机理还不清楚。本项目拟对PCAT-1促进前列腺癌细胞增殖等功能进行深入研究，阐释其在前列腺癌细胞中调控作用的模式及分子机制。本项目首先将研究两种多梳抑制复合物与PCAT-1的调控关系，证实EED亚基协调两种多梳抑制复合物共同调控PCAT-1的功能并阐明其机理；然后研究PCAT-1、多梳抑制复合物1亚基及BRCA2、c-Myc之间的相互作用；最后研究多梳抑制复合物1亚基参与PCAT-1功能行使可能相关的信号通路。本项目的完成将加深对于长链非编码RNA在前列腺癌中功能的理解，为今后开发新的生物标记物并应用于前列腺癌的早期筛查及靶向治疗提供依据，具有重要的科学意义。

中文关键词： 长链非编码RNA；前列腺癌；多梳抑制复合物；相互作用；生物标记物

英文摘要： Long non-coding RNAs play important roles in tumoregenesis、tumor progression and metastasis, which is invaluable in its application in the early diagnosis and treatment of cancer. Long non-coding RNA PCAT-1 exhibits high expression level in metastatic prostate cancer cells and promotes the proliferation of cancer cells through regulating c-myc and brca2 genes, while the mechanism is still not clear. In this project the function of PCAT-1 in promoting the proliferation of prostate cancer cells will be further studied，and the function model as well as the molecular mechanism will be interpreted in detail. Firstly we will study the regulatory relationship between two polycomb repressive complexes and PCAT-1, proving EED subunit orchestrating the two complexes to regulate PCAT-1 and its mechanism. Then we will study the interaction between PCAT-1、polycomb repressive complex 1 subunits with BRCA2 and c-Myc and analyze the mechanism. Finally we will study polycomb repressive complex 1 subunits taking part in the function of PCAT-1 in prostate cancer and the possible signal pathways involved. The completion of this project will deepen the understanding of the function of long non-coding RNAs in prostate cancer, and has important scientific significance in providing evidences for developing and applying new biomarkers in early diagnosis and targeted therapy of prostate cancer in the future.

英文关键词： long non-coding RNA;prostate cancer;polycomb repressive complex;interaction;biomarker