SNRPB通过调控RAB26可变剪接促进非小细胞肺癌进展的作用及机制研究

SNRPB是组成剪接小体的核心元件之一，在控制pre-mRNA的可变剪接过程中有重要作用。目前，关于SNRPB在肿瘤中的研究较少，其在NSCLC中的功能及作用机制仍需深入研究。我们的前期实验结果表明SNRPB在NSCLC中高表达且与病人预后不良相关。通过细胞和动物实验我们发现SNRPB在调控NSCLC细胞增殖、侵袭和迁移及肿瘤生长和转移过程中具有重要作用。进一步，我们发现SNRPB可调节下游基因RAB26的mRNA第7号内含子的可变剪接，进而通过激活无义介导的mRNA降解方式调控RAB26的表达。下一步，我们计划通过分离纯化RAB26相关分泌小泡，并通过质谱分析鉴定RAB26相关分泌小泡中的关键蛋白，研究其在SNRPB-RAB26轴在促进NSCLC进展过程中的作用。本课题的完成将证实SNRPB在NSCLC中的功能并阐明其调控下游基因RAB26表达的全新机制，将为NSCLC治疗提供新的靶点。

SNRPB is a core component of spliceosome and plays a major role in regulating alternative splicing of the pre-mRNA. To date, little is known about its role in tumor, the oncogenic function of SNRPB in NSCLC and the underling mechanisms remain to be elucidated. Our preliminary data indicates that SNRPB is overexpressed in NSCLC and predicts a poor prognosis in patients with NSCLC. We found that SNRPB promotes NSCLC cells proliferation, invasion and migration by in vitro study. In addition, we found that SNRPB promotes tumor growth and metastasis by in vivo study. Moreover, we found that SNRPB regulates alternative splicing of intron 7 in the RAB26 mRNA and the expression of RAB26 by activating nonsense-mediated mRNA decay (NMD). Next, we will isolate and purify the RAB26-related secretory vesicles and identify the key proteins via LC-MS/MS analysis. Furthermore, we will investigate the potential roles of these key proteins in SNRPB-RAB26 axis-mediated progression of NSCLC. Our study will verify the oncogenic function of SNRPB in NSCLC and elucidate the novel mechanism by which SNRPB regulates the expression of RAB26. Our study unveils SNRPB as a new therapeutic vulnerability in NSCLC cancers.