The long non-coding RNA PCSEAT exhibits an oncogenic property in prostate cancer and functions as a competing endogenous RNA that associates with EZH2

被引:37
作者
Yang, Xiaohui [1 ,2 ]
Wang, Liang [3 ]
Li, Rong [2 ]
Zhao, Yuhui [3 ]
Gu, Yinmin [2 ]
Liu, Siying [2 ]
Cheng, Tianyou [4 ]
Huang, Kuohsiang [2 ]
Yuan, Yi [5 ]
Song, Dalong [5 ]
Gao, Shan [2 ,4 ,5 ]
机构
[1] Shanghai Univ, Sch Life Sci, Lab Noncoding RNA & Canc, Shanghai 200444, Peoples R China
[2] Chinese Acad Sci, CAS Key Lab Biomed Diagnost, Suzhou Inst Biomed Engn & Technol, Suzhou 215163, Peoples R China
[3] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China
[4] Shanxi Acad Adv Res & Innovat, Taiyuan 030032, Shanxi, Peoples R China
[5] Guizhou Univ, Coll Med, Guiyang 550025, Guizhou, Peoples R China
基金
中国国家自然科学基金; 国家重点研发计划;
关键词
Prostate cancer; PCSEAT; EZH2; Competing endogenous RNA; Exosome; CELLS; EXOSOMES; GENOMICS;
D O I
10.1016/j.bbrc.2018.05.157
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Prostate cancer (PCa) is the most common malignancy and the leading cause of cancer deaths in males. Recent studies demonstrate that long non-coding RNAs (lncRNAs) are involved in many aspects of PCa. However, their biological roles in PCa remain imperfectly understood. Here, we characterized an IncRNA, PCa specific expression and EZH2-associated transcript (PCSEAT, annotated as PRCAT38), which is specifically overexpressed in PCa. We further demonstrated that knockdown of PCSEAT results in the reduction of PCa cell growth and motility, and overexpression of PCSEAT reverses these phenotypes. Furthermore, bioactive PCSEAT is incorporated into exosomes and transmitted to adjacent cells, thus promoting cell proliferation and motility. Mechanistically, we found that PCSEAT promotes cell proliferation, at least in part by affecting miR-143-3p- and miR-24-2-5p-mediated regulation of EZH2, suggesting that PCSEAT and EZH2 competitively 'sponge' miR-143-3p and miR-24-2-5p. Overall, our results reveal that PCSEAT is specifically overexpressed in PCa patients and a potential oncogene in PCa cells via mediating EZH2 activity, indicating that PCSEAT may be a potential therapeutic target in PCa. (C) 2018 Elsevier Inc. All rights reserved.
引用
收藏
页码:262 / 268
页数:7
相关论文
共 32 条
[1]   A comparative analysis of lncRNAs in prostate cancer exosomes and their parental cell lines [J].
Ahadi, Alireza ;
Khoury, Samantha ;
Losseva, Maria ;
Nham Tran .
GENOMICS DATA, 2016, 9 :7-9
[2]   Long non-coding RNAs harboring miRNA seed regions are enriched in prostate cancer exosomes [J].
Ahadi, Alireza ;
Brennan, Samuel ;
Kennedy, Paul J. ;
Hutvagner, Gyorgy ;
Nham Tran .
SCIENTIFIC REPORTS, 2016, 6
[3]   Understanding diagnostic tests 3: receiver operating characteristic curves [J].
Akobeng, Anthony K. .
ACTA PAEDIATRICA, 2007, 96 (05) :644-647
[4]   Prostate cancer [J].
Attard, Gerhardt ;
Parker, Chris ;
Eeles, Ros A. ;
Schroder, Fritz ;
Tomlins, Scott A. ;
Tannock, Ian ;
Drake, Charles G. ;
de Bono, Johann S. .
LANCET, 2016, 387 (10013) :70-82
[5]  
Chang Z., 2016, CHINESE SCI BULL, V61, P3079
[6]   An integrated encyclopedia of DNA elements in the human genome [J].
Dunham, Ian ;
Kundaje, Anshul ;
Aldred, Shelley F. ;
Collins, Patrick J. ;
Davis, CarrieA. ;
Doyle, Francis ;
Epstein, Charles B. ;
Frietze, Seth ;
Harrow, Jennifer ;
Kaul, Rajinder ;
Khatun, Jainab ;
Lajoie, Bryan R. ;
Landt, Stephen G. ;
Lee, Bum-Kyu ;
Pauli, Florencia ;
Rosenbloom, Kate R. ;
Sabo, Peter ;
Safi, Alexias ;
Sanyal, Amartya ;
Shoresh, Noam ;
Simon, Jeremy M. ;
Song, Lingyun ;
Trinklein, Nathan D. ;
Altshuler, Robert C. ;
Birney, Ewan ;
Brown, James B. ;
Cheng, Chao ;
Djebali, Sarah ;
Dong, Xianjun ;
Dunham, Ian ;
Ernst, Jason ;
Furey, Terrence S. ;
Gerstein, Mark ;
Giardine, Belinda ;
Greven, Melissa ;
Hardison, Ross C. ;
Harris, Robert S. ;
Herrero, Javier ;
Hoffman, Michael M. ;
Iyer, Sowmya ;
Kellis, Manolis ;
Khatun, Jainab ;
Kheradpour, Pouya ;
Kundaje, Anshul ;
Lassmann, Timo ;
Li, Qunhua ;
Lin, Xinying ;
Marinov, Georgi K. ;
Merkel, Angelika ;
Mortazavi, Ali .
NATURE, 2012, 489 (7414) :57-74
[7]  
Eduard W., 2016, SCI REP, V6
[8]  
Feng J., 2011, CURR PROTOC BIOINFOR, V2, p2.14.1, DOI DOI 10.1002/0471250953.BI0214-34
[9]   Long non-coding RNAs with low expression levels in cells are enriched in secreted exosomes [J].
Gezer, Ugur ;
Ozgur, Emre ;
Cetinkaya, Merve ;
Isin, Mustafa ;
Dalay, Nejat .
CELL BIOLOGY INTERNATIONAL, 2014, 38 (09) :1076-1079
[10]   As we wait: coping with an imperfect nomenclature for extracellular vesicles [J].
Gould, Stephen J. ;
Raposo, Graca .
JOURNAL OF EXTRACELLULAR VESICLES, 2013, 2 (01)