组蛋白去乙酰化酶HDAC3可促进肿瘤恶性生长，我们前期发现HDAC3表达与卵巢癌进展密切相关；发生转移的卵巢癌组织相对于未转移的卵巢癌组织高表达HDAC3，且依赖HDAC3促进肿瘤的侵袭转移；卵巢癌细胞中HDAC3与转录因子FoxA1相互结合；qPCR检测证明，下调HDAC3可降低HE4的表达，且HE4基因启动子区存在FoxA1结合位点。因此我们提出假说：“HDAC3协同FoxA1转录激活HE4表达，可能是促进卵巢癌侵袭转移的机制之一”。本项目拟在前期研究的基础上，深入探讨HDAC3/ FoxA1蛋白复合体通过表观修饰和转录激活双重调控，促进HE4表达及其在卵巢癌侵袭转移中的分子机制。研究结果有望为抑制卵巢癌的侵袭转移提供新的干预靶点和实验依据。

We recently found that overexpression of HDAC3 correlated with progression of ovarian cancer. Highly metastatic ovarian carcinoma cells exhibited upregulated level of HDAC3 and relied on HDAC3 to promote invasion and metastasis. Moreover, HDAC3 was identified to interact with a transcription factor FoxA1. By mRNA profiling and qPCR analysis, we found that knockdown of HDAC3 in highly metastatic ovarian carcinoma cells led to reduced mRNA level of HE4, whose promoter contained several FoxA1 consensus binding sites. Since transcription factor FoxA1 has been shown to be a crucial regulator for metastasis in several types of malignancies, we hypothesize that HDAC3 may act in synergy with FoxA1 to promote HE4 transcription and thus maintain stemness of highly metastatic ovarian carcinoma cells. We propose that the novel HDAC3/FOXA1 protein complex might activate HE4 expression by a cooperative manner involving both epigenetic modification and transcriptional regulation. Together, these anticipated findings may identify promising intervention targets to inhibit invasion and metastasis and thereby the uncontrolled growth of ovarian cancers.