The RNA-Binding Protein QKI Suppresses Cancer-Associated Aberrant Splicing
文献类型：期刊论文
| 作者 | Zong, FY; Fu, X; Wei, WJ; Luo, YG; Heiner, M; Cao, LJ; Fang, ZY; Fang, R; Lu, DR; Ji, HB |
| 刊名 | PLOS GENETICS
 |
| 出版日期 | 2014 |
| 卷号 | 10期号:4页码:e1004289-e1004289 |
| 通讯作者 | Zong, FY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Mol Biol, Shanghai, Peoples R China.,jyhui@sibcb.ac.cn |
| 英文摘要 | Lung cancer is the leading cause of cancer-related death worldwide. Aberrant splicing has been implicated in lung tumorigenesis. However, the functional links between splicing regulation and lung cancer are not well understood. Here we identify the RNA-binding protein QKI as a key regulator of alternative splicing in lung cancer. We show that QKI is frequently down-regulated in lung cancer, and its down-regulation is significantly associated with a poorer prognosis. QKI-5 inhibits the proliferation and transformation of lung cancer cells both in vitro and in vivo. Our results demonstrate that QKI-5 regulates the alternative splicing of NUMB via binding to two RNA elements in its pre-mRNA, which in turn suppresses cell proliferation and prevents the activation of the Notch signaling pathway. We further show that QKI-5 inhibits splicing by selectively competing with a core splicing factor SF1 for binding to the branchpoint sequence. Taken together, our data reveal QKI as a critical regulator of splicing in lung cancer and suggest a novel tumor suppression mechanism involving QKI-mediated regulation of the Notch signaling pathway. |
| 学科主题 | Genetics & Heredity |
| 类目[WOS] | Genetics & Heredity |
| 关键词[WOS] | MESSENGER-RNA ; LUNG-CANCER ; NUMB ISOFORMS ; OLIGODENDROCYTE DIFFERENTIATION ; CRITICAL REGULATOR ; GENE-EXPRESSION ; STAR PROTEIN ; QUAKING ; NOTCH ; IDENTIFICATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000335499600041 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/169]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Zong, FY,Fu, X,Wei, WJ,et al. The RNA-Binding Protein QKI Suppresses Cancer-Associated Aberrant Splicing[J]. PLOS GENETICS,2014,10(4):e1004289-e1004289. |
| APA | Zong, FY.,Fu, X.,Wei, WJ.,Luo, YG.,Heiner, M.,...&Hui, JY.(2014).The RNA-Binding Protein QKI Suppresses Cancer-Associated Aberrant Splicing.PLOS GENETICS,10(4),e1004289-e1004289. |
| MLA | Zong, FY,et al."The RNA-Binding Protein QKI Suppresses Cancer-Associated Aberrant Splicing".PLOS GENETICS 10.4(2014):e1004289-e1004289. |
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