Onecut2(OC-2)是1999年新发现的转录因子。OC-2在多种肿瘤组织中异常表达，与肿瘤的生长、调控和转移密切相关。我们发现OC-2在高转移性卵巢癌中OC-2高表达，并发现OC-2是miR6086的直接作用靶点，是VEGF的上游调控因子，调控肿瘤血管新生和转移。干扰OC-2的表达可显著抑制肿瘤生长和转移、抑制肿瘤血管新生。本研究拟进一步通过CRISPR/Cas9从卵巢癌细胞水平和小鼠动物水平敲出OC-2基因，通过iTRAQ与LC-MS/MS质谱、western-blot、免疫组化、过表达和干扰RNA等技术分析OC-2在血管新生因子网络之间的调控关系，在肿瘤血管新生、凋亡、转移等相关信号通路中的作用；体内分析OC-2对肿瘤的生长、发生、转移、血管新生、微环境等的影响；进而揭示OC-2在肿瘤生长、肿瘤转移和肿瘤发生中的调控作用与分子机制。

Onecut2 (OC-2) was found in 1999 as a transcription factor. The research showed that OC-2 was aberrant expressed in different tumors and closely related with tumor growth and metastasis. Our research found that OC-2 was high expressed in ovarian cancer, OC-2 is the target of miR6086 and the upstream regulatory factor of VEGF, which regulate the tumor angiogenesis and tumor metastasis. Silent OC-2 could significantly inhibit tumor growth and tumor angiogenesis. This project is to edit OC-2 gene in ovarian cancer cells and mice by CRISPR/Cas9, to assay the relationship of OC-2 and angiogenic factors, MicroRNA，and signal pathways of apoptosis and metastasis by iTRAQ and LC-MS/MS analysis, the technology of western-blot, immunohistochemistry, overexpression and interfering RNA to assay the proliferation, migration, invasion, apoptosis, tumor growth and metastasis, tumor angiogenesis, tumor microenvironment in vitro and in vivo, to reveal the role and molecular mechanism of OC-2 in tumor angiogenesis, metastasis and tumorigenesis.