剪接因子SRSF1对子宫内膜癌糖代谢的调控及作用机制

Endometrial carcinoma is one of the most common malignant tumors in female reproductive system, but the specific mechanism is unknown. More and more study indicate that RNA splicing plays important roles in the process of the occurrence and development of many tumors. SRSF1 of splicing factor participates in a variety of malignant tumors. However, its mechanism in the endometrial carcinoma is currently unknown. Our preliminary data suggest that the RNA and protein expression level of SRSF1 are higher in the endometrial carcinoma than in normal endometrium. The result of tissue microarray included 256 cases of EC reveal that the protein expression level of SRSF1is higher in higher grade squamous carcinoma and clear cell carcinoma. It interfered with siRNA can restrain the proliferation and invasion of endometrial carcinoma cells, reduce the sugar metabolism related indicators such as lactate secretion and glucose consumption; the proliferation and invasion of SRSF1 in endometrial carcinoma cells can been reversed treated with the glycolysis inhibitors. This study will further explicit the function of SRSF1 and possible target gene splicing in endometrial carcinoma by the RNA-seq etal., to clear SRSF1 function in the EC and may control the target genes of spliceosome, to explore the molecular mechanisms of SRSF1 how to affect EC sugar metabolism. This study will lay a foundation for further revealing the pathogenesis of the endometrial carcinoma, provides new ideas for its effective prevention and control.

子宫内膜癌（endometrial carcinoma，EC）是女性生殖系统中最常见的肿瘤之一，但发病机理不清。越来越多研究表明RNA剪接在肿瘤发生、发展过程中发挥作用。SRSF1作为剪接因子的一种，参与多种恶性肿瘤进展，然而它在EC中的作用及机制目前未知。我们前期研究发现，与正常子宫内膜相比，SRSF1的RNA和蛋白表达水平在EC中异常升高；对256例EC组织芯片染色发现，在恶性度较高的鳞癌、透明细胞癌者中SRSF1蛋白表达量更高； siRNA干扰其表达，能抑制EC细胞的增殖和侵袭行为、降低糖代谢相关指标如乳酸分泌量和葡萄糖消耗量；加入糖酵解抑制剂能逆转SRSF1对EC细胞的作用。本研究将进一步采用转录组测序等方法，明确SRSF1在EC中的功能及可能调控的靶基因剪接体，深入探讨SRSF1通过怎样的分子机制影响EC糖代谢。本研究将为进一步揭示EC发病机制奠定基础，为其有效防治提供新思路。