选择性剪接（alternative splicing）是产生蛋白质组多样性的重要机制，并与肿瘤的发生、发展密切相关。丝氨酸/精氨酸富集剪接因子1（serine/arginine-rich splicing factor 1，SRSF1）是选择性剪接因子家族的代表性成员，参与前体mRNA的选择性剪接与加工、胞内定位与运输等生理过程。研究已证实，SRSF1为原癌蛋白，并在肺癌、乳腺癌和白血病等人类肿瘤细胞中存在过表达现象。SRSF1蛋白通过与肿瘤相关基因的相互作用、调控细胞周期及凋亡等多种途径参与肿瘤的发生、发展过程。此外，SRSF1蛋白通过影响PI3K-Akt-mTOR、Ras-MNK-MAPK及Wnt-β-catenin信号转导通路中相关基因的剪接方式发挥致癌作用。针对剪接异常事件，目前主要采用反义寡核苷酸方法特异性纠正基因的错误性剪接，该方法已在肺癌及乳腺癌等实体肿瘤治疗中开展研究。深入研究选择性剪接的位点选择机制和作用机制必将对探讨肿瘤发病机制、诊断和治疗方法产生深远影响。

Alternative splicing of pre-mRNA is an important mechanism of the proteomic diversity, and is closely related to the cancer development. Serine/arginine-rich splicing factor 1 (SRSF1), a typical member of alternative splicing family, is involved in diverse events including alternative splicing and processing, intracellur location and transportation of precursor mRNA. SRSF1 has been identified as an oncoprotein and is up-regualted in many cancers, including those of the lung, breast, as well as in leukemia. SRSF1 contributes to tumorigenesis and development by interacting with cancer-related genes, regulating cell cycle and apoptosis and other cell processes. Additionally, SRSF1 plays an oncogenic role through regulating the splicing of genes involved in several signaling pathways including PI3K-Akt-mTOR, Ras-MNK-MAPK and Wnt-β-catenin. For splicing disorders, the current treatment is to correct the missplicing of genes with antisense oligonucleotides, which has been widely applied in some solid tumors such as lung cancer and breast cancer. On this basis, further exploration in site selection and mechanism of alternative splcing will elucidate tumorigenesis and improve the diagnosis and treatment of cancer.

国家自然科学基金资助项目（No. 81070454）; 北京市卫生系统高层次卫生技术人才培养计划资助项目（No. 2011-2-11）