MicroRNA-101调控CRMP4表达抑制前列腺癌转移的机制研究

Metastasis is the main cause for the death of prostate cancer (PCa). The applicant firstly improved that CRMP4 is a novel metastasis suppressor of PCa, and trimethylation of histone H3K27 in its promoter control the expression of CRMP4. Recent researches found that miRNA played very important role in histone modification. Science reported that miR-101 regulated trimethylation of histone H3K27 in PCa through EZH2, and the genomic loss of miR-101 led to PCa progression. It is not clear whether and how miR-101 inhibit metastasis of PCa. The applicant speculates that miR-101 might down-regulate CRMP4 by trimethylation of histone H3K27 to surpress the metastasis of PCa. This research aims to investigate the relation among miR-101, EZH2 and CRMP4 in PCa. Transfect miR-101 into PCa cells to make sure whether miR-101 regulate the expression of CRMP4 in order to clarify the regulatory mechanism of CRMP4, to make sure whether up-regulation of CRMP4 through miR-101 inhibit the invasion and metastasis of PCa which would provide new evidence on the inhibition of metastasis of PCa through miR-101.

转移是前列腺癌(PCa)患者死亡的主要原因。申请人首次证实CRMP4是新的PCa转移抑制基因，进一步研究发现其启动子组蛋白H3K27三甲基化等修饰调控了CRMP4的表达。最近研究发现miRNA在调控组蛋白修饰方面发挥重要作用。Science报道miR-101通过EZH2调控PCa组蛋白H3K27三甲基化，其基因缺失导致PCa进展。但miR-101是否抑制PCa转移及其机制目前尚不明确。申请人推测miR-101可能通过调控CRMP4组蛋白H3K27三甲基化使其表达下调进而抑制PCa转移。本项目拟分析miR-101、EZH2及CRMP4在PCa中表达的相关性；miR-101转染PCa细胞，明确miR-101是否可调控CRMP4的表达，进一步阐明CRMP4的调控机制；体内、体外实验明确miR-101上调CRMP4表达后是否可抑制PCa的侵袭和转移，为miR-101抑制PCa转移提供新的科学依据。