ZIC2上调SOX2表达对促进前列腺癌转移的作用机制探讨

肿瘤复发和转移是决定患者预后和死亡的关键因素。我国转移性前列腺癌较多，对调控前列腺癌转移关键基因作用及机制的研究有重要意义。癌基因ZIC2能增加肿瘤侵袭及转移能力，前期研究显示前列腺癌中ZIC2高表达与预后不良相关。前列腺癌中SOX2高表达增加癌细胞侵袭和迁移能力，ZIC2下调将导致SOX2蛋白表达降低，SOX2可能是ZIC2调节前列腺癌发生侵袭及转移下游基因。检测癌组织中ZIC2及SOX2表达；利用RNAi、基因过表达及双荧光素酶载体等方法探讨体内外前列腺癌细胞侵袭、转移力变化，明确ZIC2及SOX2对该变化的影响；检测SOX2受ZIC2上调后对前列腺癌干细胞干性变化、维持EMT间质特性，证实ZIC2上调SOX2能增强前列腺癌干细胞间质性造成侵袭及转移。本课题将明确SOX2是否为ZIC2靶基因；阐明SOX2受ZIC2靶向上调诱导前列腺癌侵袭和转移，为该疾病诊治提供新靶点及预后监测依据。

Recurrence and metastasis of malignant tumors are the key factors that determine the prognosis and death of patients. Metastatic prostate cancers is high in China, and it is of great significance to study the function and mechanism of regulating prostate cancer metastasis. Invasion and metastasis of malignance will be promoted by oncogene ZIC2 . Previous studies have shown that high ZIC2 expression is associated with poor prognosis in prostate cancer. High expression of SOX2 in prostate cancer increases the invasion and migration of cancer cells. Decrease expression of SOX2 protein will be led by down-regulation of ZIC2 in the prostate cancer cells. SOX2 may be involved as downstream genes of ZIC2 regulated in. To determine the effect of ZIC2 and SOX2 on this change of invasion and metastasis of prostate cancer, by constructing RNAi, gene overexpression, and dual luciferase vectors, the ability of invasion and metastasis of prostate cancer cells was examined in vitro and in vivo; and the detection of SOX2 upregulation in prostate cancer stem cells by ZIC2 upregulation, maintenance of EMT mesenchymal properties, confirmed that upregulation of SOX2 by ZIC2 enhanced prostate cancer stem cell mesenchymal invasion and metastasis. This research will clarify whether SOX2 is a target gene of ZIC2; elucidate that SOX2 is induced by ZIC2 up-regulation to promote the invasion and metastasis of prostate cancer; and provide a new target for the diagnosis and treatment of this disease and its prognostic monitoring basis.