Fli-1激动剂抑制前列腺癌细胞生长、转移与侵袭的分子机制

Fli-1基因是E26家族转化特异性转录因子，参与调控细胞增殖、分化以及凋亡在内的多种生理过程的关键基因的表达。前期研究发现在恶性病变程度越高的前列腺癌组织中Fli-1表达越低，表明Fli-1在前列腺癌发展过程中可能是一种抑癌基因，其诱导表达可抑制前列腺癌发展；利用建立的启动子筛选策略，获得了5个天然产物来源的Fli-1激动剂，但不确定化学诱导Fli-1表达可否在体内有效抑制前列腺癌发展及其作用的分子机制仍不清楚。本项目拟构建Fli-1过表达及弱表达的癌细胞及动物模型，研究确定利用Fli-1激活剂调控前列腺癌发展的有效性；基于Fli-1靶基因，癌症发展相关因子，WNT、PI3K-Akt、VEGF信号通路及转录组学技术研究Fli-1激动剂处理细胞中的差异基因，解析其调控网络途径，阐明Fli-1激活剂影响前列腺癌发展的分子机制，为研发靶向调控Fli-1的抗前列腺癌药物奠定基础和新方法。

Fli-1 gene, as the transformation-specific transcription factor of E26 family, involves in regulating the expression of key genes in the multiple physiological process including cell growth, differentiation and apoptosis. Previous study found that the Fli-1 may be as a tumor suppressor gene in the development of prostate cancer its inducing expression can inhibit the development of prostate cancer. There were five Fli-1 agonists was obtained from the natural products using established screening strategy of the promoter, however, it is not sure that its promotion for the expression of Fli-1 whether can effectively restrain the development of prostate cancer in vivo and its molecular mechanism remains unclear. This project intends to establish the cancer cell and animal models of overexpression and slight-expression of Fli-1 agonists, to investigate the efficacy of controlling the development of prostate cancer using Fli-1 agonists. Based on the FLi-1 target genes, the related factors of cancer development, WNT, PI3K-Akt, VEGF signaling pathways and transcriptomics technology, we assayed the differential genes in the treated cells with Fli-1 agonists, analyze the regulation network pathways, clarify the molecular mechanism for affecting the development of prostate cancer using Fli-1 agonists, which will lay the foundation and provide a new method for developing the drug of prostate cancer that targeted Fli-1.