RNA-binding protein YBX1 promotes cell proliferation and invasiveness of nasopharyngeal carcinoma cells via binding to AURKA mRNA.
RNA-binding protein YBX1 promotes cell proliferation and invasiveness of nasopharyngeal carcinoma cells via binding to AURKA mRNA.
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RNA结合蛋白YBX1通过与AURKA mRNA结合促进鼻咽癌细胞的细胞增殖和侵袭。
DOI：
10.7150/jca.56262
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发表时间：
2021
影响因子：
3.9
通讯作者：
Yi M
中科院分区：
文献类型：
--
作者：
Ban Y;Tan Y;Li X;Li X;Zeng Z;Xiong W;Li G;Xiang B;Yi M
背景：RNA结合蛋白（RBP）在基因表达的转录后调控中起重要作用。RBP的失调与人类疾病（包括癌症）的发展和进展密切相关。然而，鼻咽癌（NPC），这是一个独特的亚型的头颈癌，RBP的作用仍然难以捉摸。方法：通过分析GEO数据库和交联免疫沉淀获得的高通量蛋白质组数据，对NPC相关RBP进行研究。免疫组化法检测鼻咽癌组织中Y盒结合蛋白1（YBX 1）的表达水平。Kaplan-Meier Plotter分析YBX 1蛋白表达水平与鼻咽癌患者预后的关系。RNA干扰抑制鼻咽癌细胞中YBX 1的表达水平。CCK-8法测定细胞生长情况。细胞迁移率和侵袭力通过transwell测定。通过使用异种移植肿瘤测定来测量致瘤性。mRNA或蛋白质的表达水平分别通过qPCR或蛋白质印迹测定来确定。通过RNA免疫沉淀（RIP）和qPCR测定与YBX 1结合的mRNA。荧光素酶报告基因检测YBX 1对mRNA翻译的影响。结果：在本研究中，我们证明了鼻咽癌和正常对照之间的差异表达的RBPs谱。在这些异常表达的RBPs中，YBX 1在NPC中过表达。我们发现YBX 1主要定位于NPC细胞的细胞质中。YBX 1的缺失导致体外细胞增殖、迁移和侵袭能力降低，体内致瘤性降低。YBX 1的过表达与细胞周期G2/M检查点调节剂的高表达相关。此外，YBX 1通过直接结合其mRNA促进AURKA蛋白表达。YBX 1的缺失导致AURKA蛋白水平的降低。AURKA的强制表达挽救了YBX 1沉默的NPC细胞中的细胞增殖和侵袭力。结论：YBX 1通过促进AURKA蛋白的合成，促进鼻咽癌细胞的增殖和侵袭力。
Background: RNA-binding proteins (RBPs) play essential roles in post-transcriptional control of gene expression. Dysregulation of RBPs is intensively implicated in development and progression of human diseases, including cancers. However, the roles of RBPs in nasopharyngeal carcinoma (NPC), which is a distinct subtype of head and neck cancer, remain elusive. Methods: NPC-related RBPs were explored by analyzing GEO database and high-throughput proteomic data obtained from crosslinking immunoprecipitation. The expression levels of Y box binding protein 1 (YBX1) protein in NPC samples were measured by immunohistochemistry (IHC) staining. The association of YBX1 protein levels with prognosis of NPC patients was analyzed by Kaplan-Meier Plotter. The expression levels of YBX1 in NPC cells were inhibited by RNA interference. Cell growth was measured by CCK-8 assay. Cell mobility and invasiveness were measured by transwell assays. Tumorigenicity was measured by using a xenograft tumor assay. The expression levels of mRNAs or proteins were determined by qPCR or western blot assays, respectively. The mRNAs binding to YBX1 were determined by RNA immunoprecipitation (RIP) and qPCR. The effect of YBX1 on mRNA translation was measured by luciferase reporter assay. Results: In the present study, we demonstrated a differentially expressed RBPs profile between NPC and its normal counterpart. Among these aberrantly expressed RBPs, YBX1 was overexpressed in NPC. We found that YBX1 is mainly localized in the cytoplasm of NPC cells. Loss of YBX1 led to reduced cell proliferation, migration and invasiveness in vitro, and reduced tumorigenicity in vivo. Overexpression of YBX1 associates with high expression of cell cycle G2/M checkpoint modulators. In addition, YBX1 promotes AURKA protein expression by directly binding to its mRNA. Loss of YBX1 leads to reduction of AURKA protein level. Forced expression of AURKA rescues cell proliferation and invasiveness in YBX1-silenced NPC cell. Conclusions: The current study indicated that YBX1 promotes NPC cell proliferation and invasiveness through enhancing protein synthesis of AURKA.
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影响因子：
8
作者：
Aparicio, Luis A.;Abella, Vanessa;Valladares, Manuel;Figueroa, Angelica
通讯作者：
Figueroa, Angelica
GEPIA：用于癌症和正常基因表达谱和交互式分析的网络服务器。
影响因子：
14.9
作者：
Tang Z;Li C;Kang B;Gao G;Li C;Zhang Z
通讯作者：
Zhang Z
影响因子：
10.3
作者：
Lasham, Annette;Samuel, Weini;Braithwaite, Antony W.
通讯作者：
Braithwaite, Antony W.
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影响因子：
6.6
作者：
Ban, Yuanyuan;Tan, Pingqing;Xiang, Bo
通讯作者：
Xiang, Bo
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影响因子：
2.9
作者：
Zhu, Hong-Ming;Fei, Qian;Yin, Li
通讯作者：
Yin, Li