RNA可变剪接在肿瘤进展中发挥重要作用，其中剪接因子与肿瘤的关系尤为密切，但剪接因子RBM7与肿瘤的关系尚未有报道。我们前期研究结果显示RBM7在乳腺癌组织中高表达；敲降RBM7抑制肿瘤细胞增殖与迁移，以及裸鼠皮下移植瘤的生长。在前期研究工作基础上结合我们在RNA相关疾病方面的研究背景（Molecular Therapy，2014），本项目拟从细胞、临床组织样本和小鼠在体水平多层次系统性探究RBM7在乳腺癌发生发展中调控恶性表型的功能；利用RNA可变剪接报告基因系统和优化的人工合成剪接因子（Nucleic Acids Research，2018）等阐明RBM7调控可变剪接的机制，通过高通量测序鉴定RBM7调控的肿瘤相关基因的可变剪接事件，并进一步解析其在肿瘤进展中的分子作用机制；明确RBM7在乳腺癌组织中高表达的临床意义及临床应用价值。本项目的实施将为乳腺癌的治疗提供潜在的新靶标和新思路。

Dysregulation of RNA alternative splicing contributes to tumorigenesis. Specifically, splicing factors are closely associated with cancer progression, however, there is no related report about RBM7 and cancer. Our previous data demonstrated that RBM7 is up-regulated in breast cancers. In addition, knockdown of RBM7 suppresses proliferation and migration of MDA-MB-231 cells, as well as the growth of xenograft tumors. Based on our preliminary results in combination with our research background on RNA related diseases（Molecular Therapy, 2014）, we will apply cell culture model, in vivo mice model and clinical analyses to systematically study the role of RBM7 during cancer progression. Using the classic GFP reporter gene system and the optimized engineered splicing factors（Nucleic Acids Research, 2018）, we will investigate how RBM7 regulates alternative splicing. Through the high throughput RNA-sequencing, we will identify the alternative splicing events regulated by RBM7 and determine the underlying molecular mechanisms. Moreover, we will clarify its clinical significance for breast cancer patients. Collectively, this study will provide novel therapeutic targets and a new approach for future cancer therapy.