Nuclear PTEN safeguards pre-mRNA splicing to link Golgi apparatus for its tumor suppressive role
文献类型:期刊论文
作者 | Shen, Shao-Ming3; Zhang, Cheng3; Yang, Shuo3; Xiong, Zhong3; Ge, Meng-Kai3; Yu, Yun3; Xia, Li3; Guo, Meng3; Liu, Jun-Ling3,4; Yu, Jian-Xiu3,4 |
刊名 | NATURE COMMUNICATIONS
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出版日期 | 2018 |
卷号 | 9期号:-页码:2392 |
ISSN号 | 2041-1723 |
DOI | 10.1038/s41467-018-04760-1 |
文献子类 | Article |
英文摘要 | Dysregulation of pre-mRNA alternative splicing (AS) is closely associated with cancers. However, the relationships between the AS and classic oncogenes/tumor suppressors are largely unknown. Here we show that the deletion of tumor suppressor PTEN alters pre-mRNA splicing in a phosphatase-independent manner, and identify 262 PTEN-regulated AS events in 293T cells by RNA sequencing, which are associated with significant worse outcome of cancer patients. Based on these findings, we report that nuclear PTEN interacts with the splicing machinery, spliceosome, to regulate its assembly and pre-mRNA splicing. We also identify a new exon 2b in GOLGA2 transcript and the exon exclusion contributes to PTEN knockdown-induced tumorigenesis by promoting dramatic Golgi extension and secretion, and PTEN depletion significantly sensitizes cancer cells to secretion inhibitors brefeldin A and golgicide A. Our results suggest that Golgi secretion inhibitors alone or in combination with PI3K/Akt kinase inhibitors may be therapeutically useful for PTEN-deficient cancers. |
学科主题 | Science & Technology - Other Topics |
WOS关键词 | INTRON RETENTION ; MATRIX PROTEIN ; IN-VIVO ; CANCER ; MYELODYSPLASIA ; SPLICEOSOME ; EXPRESSION ; MUTATIONS ; APOPTOSIS ; NETWORK |
语种 | 英语 |
WOS记录号 | WOS:000435538500010 |
出版者 | NATURE PUBLISHING GROUP |
版本 | 出版稿 |
源URL | [http://202.127.25.144/handle/331004/703] ![]() |
专题 | 中国科学院上海生命科学研究院营养科学研究所 |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai 200025, Peoples R China; 2.SJTU SM, Shanghai 200025, Peoples R China; 3.Shanghai Jiao Tong Univ, Sch Med SJTU SM, Minist Educ, Key Lab Cell Differentiat & Apoptosis Chinese,Dep, Shanghai 200025, Peoples R China; 4.SJTU SM, Shanghai Key Lab Tumor Microenvironm & Inflammat, Dept Biochem & Mol Cell Biol, Shanghai 200025, Peoples R China, |
推荐引用方式 GB/T 7714 | Shen, Shao-Ming,Zhang, Cheng,Yang, Shuo,et al. Nuclear PTEN safeguards pre-mRNA splicing to link Golgi apparatus for its tumor suppressive role[J]. NATURE COMMUNICATIONS,2018,9(-):2392. |
APA | Shen, Shao-Ming.,Zhang, Cheng.,Yang, Shuo.,Xiong, Zhong.,Ge, Meng-Kai.,...&,.(2018).Nuclear PTEN safeguards pre-mRNA splicing to link Golgi apparatus for its tumor suppressive role.NATURE COMMUNICATIONS,9(-),2392. |
MLA | Shen, Shao-Ming,et al."Nuclear PTEN safeguards pre-mRNA splicing to link Golgi apparatus for its tumor suppressive role".NATURE COMMUNICATIONS 9.-(2018):2392. |
入库方式: OAI收割
来源:上海营养与健康研究所
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