SNRPB promotes the tumorigenic potential of NSCLC in part by regulating RAB26
SNRPB promotes the tumorigenic potential of NSCLC in part by regulating RAB26
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SNRPB 部分通过调节 RAB26 促进 NSCLC 的致瘤潜力
DOI：
10.1038/s41419-019-1929-y
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发表时间：
2019-09-11
影响因子：
9
通讯作者：
Zhang, Longzhen
中科院分区：
文献类型：
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作者：
Liu, Nianli;Wu, Zhiyuan;Zhang, Longzhen
SNRPB是剪接体的核心成分，在调节前体mRNA的选择性剪接中起主要作用。然而，迄今为止，人们对其在癌症中的作用知之甚少。在这项研究中，我们观察到SNRPB在NSCLC中过表达，并与NSCLC患者的不良预后相关。我们证明，SNRPB促进NSCLC肿瘤发生在体外和体内。从机制上讲，我们揭示了RAB 26是SNRPB的关键靶标。SNRPB的抑制导致RAB 26 mRNA中内含子7的保留，并通过激活无义介导的RNA衰变（NMD）减少RAB 26 mRNA。此外，RAB 26的强制表达部分恢复了SNRPB耗竭的NSCLC细胞中降低的致瘤性。我们的研究揭示了SNRPB通过调节RAB 26表达促进NSCLC肿瘤发生的新作用，并提出SNRPB/RAB 26途径可能为NSCLC提供治疗脆弱性。
SNRPB is a core component of spliceosome and plays a major role in regulating alternative splicing of the pre-mRNA. However, little is known about its role in cancer to date. In this study, we observe that SNRPB is overexpressed in NSCLC and correlated with poor prognosis in patients with NSCLC. We demonstrate that SNRPB promotes NSCLC tumorigenesis both in vitro and in vivo. Mechanistically, we reveal that RAB26 is a critical target of SNRPB. Suppression of SNRPB leads to retention of intron seven in the RAB26 mRNA and reduced RAB26 mRNA through activation of nonsense-mediated RNA decay (NMD). Moreover, forced expression of RAB26 partially restores the decreased tumorigenicity in NSCLC cells with SNRPB depletion. Our study unveils a novel role of SNRPB in facilitating NSCLC tumorigenesis via regulation of RAB26 expression and proposes that the SNRPB/RAB26 pathway may offer a therapeutic vulnerability in NSCLC.