miRNA-96-5p/TPM2促进前列腺癌循环肿瘤细胞上皮间质转化的机制研究

前列腺癌细胞经过上皮-间质转化（EMT）从原发灶脱落形成循环肿瘤细胞（CTCs）是肿瘤转移过程的重要环节。寻找并干预此过程中的关键调控分子可能为前列腺癌治疗提供新的思路。我们前期研究发现，前列腺癌患者外周血CTCs中TPM2表达较肿瘤组织明显降低；前列腺癌细胞系中miR-96-5p可以抑制TPM2的表达。由此推测miR-96-5p/TPM2通路可能在前列腺癌细胞发生EMT形成CTCs的过程中发挥关键作用。本研究拟进一步探索：1）比较前列腺癌CTCs和原发灶中基因的表达差异；2）从分子、细胞和动物水平阐明miR-96-5p/TPM2通路调控前列腺癌细胞EMT并促进CTCs形成的具体机制；3）分析前列腺癌中miR-96-5p/TPM2在CTCs中的表达水平与患者临床病理特征及预后的关系。本研究旨在阐明前列腺癌细胞发生EMT形成CTCs的分子机制，为早期干预前列腺癌转移提供新的靶点。

Metastatic prostate cancer (mPCa) accounts for nearly 58% of the newly diagnosed patients in China.Metastasis is the main cause of death in patients with prostate cancer.It is found that circulating tumor cells (CTCs) are the early process of metastasis,and the ability of CTCs subsets with different epithelial-mesenchymal transition (EMT) phenotypes to distant metastasis are different.In our preliminary experiments,we found that there was significant heterogeneity between peripheral CTCs and the primary prostate cancer tissue by gene sequencing,TPM2 expression was down-regulated in CTCs.miRNA-96-5p was detected to suppress the TPM2 expression in the prostate cancer cell lines.So we speculated the miR-96-5p/TPM2 pathway can regulate the EMT in the prostate cancer.The purpose of this study is to evaluate the role of different subpopulations of CTCs in forming distant metastasis by tumor tissue and CTCs sequencing,in vitro study and CTCs-derived animal models.It is speculated that miR-96-5p/TPM2 pathway can promote tumor cell epithelial-mesenchymal transition and form distant metastasis,so as to provide the clinical basis for the individualized diagnosis and treatment of mPCa patients.