表观遗传调控基因ARID5B在卵巢癌恶性表型中的功能及分子机制研究

表观遗传修饰是肿瘤研究热点，表观遗传相关基因为肿瘤防治新的靶点。ARID5B基因为染色体修饰蛋白，可促进组蛋白去甲基化，调节靶基因转录，其在肿瘤中的研究不多，且意见分歧，在卵巢癌中未见报道。预实验显示卵巢癌ARID5B低表达；过表达ARID5B后抑制卵巢癌细胞增殖；转录组分析发现ARID5B与PHF2结合，抑癌基因SORBS2为ARID5B下游靶基因。推测ARID5B促进SORBS2启动子组蛋白去甲基化，激活其转录，从而抑制卵巢癌细胞的恶性表型。本项目拟通过细胞及裸鼠成瘤实验明确ARID5B在卵巢癌中的生物学功能；荧光素酶、ChIP-QPCR实验探讨ARID5B调控SORBS2组蛋白甲基化的分子机制；扩大样品验证ARID5B在卵巢癌中的临床意义。本项目探讨了表观遗传相关基因ARID5B在卵巢癌细胞恶性表型中的功能、分子机制及临床意义，为明确ARID5B作为卵巢癌诊疗潜在新靶点提供理论基础。

Epigenetic modification is a hot topic in the field of cancer research, for epigenetically related genes are potential novel targets for cancer prevention and treatment. ARID5B promotes histone demethylation and regulates transcription of target genes. However, its role in cancer is relatively rare, and opinions are different. Its role in ovarian cancer has not been reported. In preliminary studies, we found significantly low expression of ARID5B in ovarian cancer, whereas overexpression of ARID5B inhibits proliferation of ovarian cancer cells. Further downstream transcriptome analysis revealed that ARID5B binds to PHF2 to form AIRID5B-PHF2 complex to regulate the expression of tumor suppressor gene SORBS2. We therefore hypothesized that ARID5B inhibits the malignant phenotype of ovarian cancer cells by inhibiting the methylation of the SORBS2 promoter histone proteins and activating SORBS2 transcription. We propose to determine the biological function of ARID5B in ovarian cancer using in vitro cell models and in vivo nude mice xenograft tumor model. We will explore the molecular mechanisms by which ARID5B regulates SORBS2 promoter methylation, using luciferase assay, ChIP-PCR and other approaches. We will also verify the clinical significance of ARID5B in ovarian cancer samples. This project will clarify the role of ARID5B as a key tumor suppressor gene in ovarian cancer, analyze the biological function, molecular mechanisms and clinical significance of ARID5B in the malignant phenotype of ovarian cancer, and provide a rationale for ARID5B as a potential new target for the diagnosis and treatment of ovarian cancer.