SNRPB promotes the tumorigenic potential of NSCLC in part by regulating RAB26

被引：48

作者：

Liu, Nianli ^{[1
,2
]}

Wu, Zhiyuan ^{[1
,2
]}

Chen, Aoxing ^{[1
]}

Wang, Yuqi ^{[1
]}

Cai, Dafei ^{[1
]}

Zheng, Junian ^{[1
,3
,4
]}

Liu, Yong ^{[1
]}

Zhang, Longzhen ^{[1
,2
]}

机构：

[1] Xuzhou Med Univ, Canc Inst, Xuzhou, Jiangsu, Peoples R China

[2] Xuzhou Med Univ, Dept Radiat Oncol, Affiliated Hosp, Xuzhou, Jiangsu, Peoples R China

[3] Xuzhou Med Univ, Affiliated Hosp, Ctr Clin Oncol, Xuzhou, Jiangsu, Peoples R China

[4] Xuzhou Med Univ, Canc Inst, Jiangsu Ctr Collaborat & Innovat Canc Biotherapy, Xuzhou, Jiangsu, Peoples R China

来源：

CELL DEATH & DISEASE | 2019年 / 10卷 / 9期

基金：

中国国家自然科学基金;

关键词：

GENE-EXPRESSION; SPLICING MACHINERY; WEB-TOOL; CANCER; MANAGEMENT; SPLICEOSOME; MUTATIONS; DATABASE; PROTEIN; GROWTH;

D O I：

10.1038/s41419-019-1929-y

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：11

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