NCBP1 promotes the development of lung adenocarcinoma through up-regulation of CUL4B
NCBP1 promotes the development of lung adenocarcinoma through up-regulation of CUL4B
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NCBP1通过上调CUL4B促进肺腺癌的发展
DOI：
10.1111/jcmm.14581
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发表时间：
2019
影响因子：
5.3
通讯作者：
He Zelai
中科院分区：
文献类型：
--
作者：
Zhang Huijun;Wang An;Tan Yulong;Wang Shaohua;Ma Qinyun;Chen Xiaofeng;He Zelai
肺癌是最常见的癌症类型，也是全球肿瘤相关死亡的主要原因。核帽结合蛋白1（NCBP 1）是加帽RNA加工和细胞内定位所必需的。据报道，NCBP 1的沉默导致HeLa细胞中的细胞生长减少。然而，其在非小细胞肺癌中的临床意义和潜在分子机制仍不清楚。在本研究中，我们发现NCBP 1在肺癌组织和几种肺癌细胞系中显著过表达。通过敲低和过表达实验，我们表明NCBP 1促进肺癌细胞生长，伤口愈合能力，迁移和上皮间质转化。从机制上讲，我们发现cullin 4 B（CUL 4 B）是NSCLC中NCBP 1的下游靶基因。NCBP 1通过与核帽结合蛋白3（NCBP 3）相互作用上调CUL 4 B表达。CUL 4 B沉默在体外显著逆转NCBP 1诱导的肿瘤发生。基于这些发现，我们提出了一个涉及NCBP 1-NCBP 3-CUL 4 B癌蛋白轴的模型，为CUL 4 B如何被激活并促进LUAD进展提供了新的见解。
Lung cancer is the most frequent cancer type and is the leading cause of tumour‐associated deaths worldwide. Nuclear cap‐binding protein 1 (NCBP1) is necessary for capped RNA processing and intracellular localization. It has been reported that silencing of NCBP1 resulted in cell growth reduction in HeLa cells. Nevertheless, its clinical significance and underlying molecular mechanisms in non–small‐cell lung cancer remain unclear. In this study, we found that NCBP1 was significantly overexpressed in lung cancer tissues and several lung cancer cell lines. Through knockdown and overexpression experiments, we showed that NCBP1 promoted lung cancer cell growth, wound healing ability, migration and epithelial‐mesenchymal transition. Mechanistically, we found that cullin 4B (CUL4B) was a downstream target gene of NCBP1 in NSCLC. NCBP1 up‐regulated CUL4B expression via interaction with nuclear cap‐binding protein 3 (NCBP3). CUL4B silencing significantly reversed NCBP1‐induced tumorigenesis in vitro. Based on these findings, we propose a model involving the NCBP1‐NCBP3‐CUL4B oncoprotein axis, providing novel insight into how CUL4B is activated and contributes to LUAD progression.