DUXAP8, a pseudogene derived lncRNA, promotes growth of pancreatic carcinoma cells by epigenetically silencing CDKN1A and KLF2

被引:61
作者
Lian, Yifan [1 ,2 ]
Yang, Jiebin [1 ,2 ]
Lian, Yikai [1 ,2 ]
Xiao, Chuangxing [1 ,2 ]
Hu, Xuezhen [3 ]
Xu, Hongzhi [1 ,2 ]
机构
[1] Xiamen Univ, Zhongshan Hosp, Dept Gastroenterol, Xiamen 361005, Fujian, Peoples R China
[2] Xiamen Univ, Inst Microbial Ecol, Xiamen 361005, Fujian, Peoples R China
[3] Nanjing Univ TCM, Affiliated Hosp, Jiangsu Prov Hosp TCM, Nanjing 210029, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Pancreatic cancer; Proliferation; Pseudogene; DUXAP8; CDKN1A; KLF2; EXPRESSED RNAS; PROLIFERATION; EZH2; LSD1; DEMETHYLATION; APOPTOSIS; BINDING;
D O I
10.1186/s40880-018-0333-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BackgroundRecent studies highlight pseudogene derived long non-coding RNAs (lncRNAs) as key regulators of cancer biology. However, few of them have been well characterized in pancreatic cancer. Here, we aimed to identify the association between pseudogene derived lncRNA DUXAP8 and growth of pancreatic cancer cells.MethodsWe screened for pseudogene derived lncRNAs associated with human pancreatic cancer by comparative analysis of three independent datasets from GEO. Quantitative real-time reverse transcription polymerase chain reaction was used to assess the relative expression of DUXAP8 in pancreatic cancer tissues and cells. Loss-of-function approaches were used to investigate the potential functional roles of DUXAP8 in pancreatic cancer cell proliferation and apoptosis in vitro and in vivo. RNA immunoprecipitation, chromosome immunoprecipitation assay and rescue experiments were performed to analyze the association of DUXAP8 with target proteins and genes in pancreatic cancer cells.ResultsPancreatic cancer tissues had significantly higher DUXAP8 levels than paired adjacent normal tissues. High DUXAP8 expression was associated with a larger tumor size, advanced pathological stage and shorter overall survival of pancreatic cancer patients. Moreover, silencing DUXAP8 expression by siRNA or shRNA inhibited pancreatic cancer cell proliferation and promoted apoptosis in vitro and in vivo. Mechanistic analyses indicated that DUXAP8 regulates PC cell proliferation partly through downregulation of tumor suppressor CDKN1A and KLF2 expression.ConclusionOur results suggest that tumor expression of pseudogene derived lncRNA DUXAP8 plays an important role in pancreatic cancer progression. DUXAP8 may serve as a candidate biomarker and represent a novel therapeutic target of pancreatic cancer.
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页数:11
相关论文
共 30 条
[1]   p21 in cancer: intricate networks and multiple activities [J].
Abbas, Tarek ;
Dutta, Anindya .
NATURE REVIEWS CANCER, 2009, 9 (06) :400-414
[2]   Aberrations of EZH2 in Cancer [J].
Chase, Andrew ;
Cross, Nicholas C. P. .
CLINICAL CANCER RESEARCH, 2011, 17 (09) :2613-2618
[3]   Long noncoding RNA HOXA-AS2 represses P21 and KLF2 expression transcription by binding with EZH2, LSD1 in colorectal cancer [J].
Ding, J. ;
Xie, M. ;
Lian, Y. ;
Zhu, Y. ;
Peng, P. ;
Wang, J. ;
Wang, L. ;
Wang, K. .
ONCOGENESIS, 2017, 6 :e288-e288
[4]   Pseudogene-Expressed RNAs: Emerging Roles in Gene Regulation and Disease [J].
Grander, Dan ;
Johnsson, Per .
LONG NON-CODING RNAS IN HUMAN DISEASE, 2016, 394 :111-126
[5]   Pseudogene PTENP1 Suppresses Gastric Cancer Progression by Modulating PTEN [J].
Guo, Xiaoqiang ;
Deng, Li ;
Deng, Kaiyuan ;
Wang, Hao ;
Shan, Ting ;
Zhou, Hong ;
Liang, Zheng ;
Xia, Jiazeng ;
Li, Chenglong .
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 2016, 16 (04) :456-464
[6]   GENCODE: The reference human genome annotation for The ENCODE Project [J].
Harrow, Jennifer ;
Frankish, Adam ;
Gonzalez, Jose M. ;
Tapanari, Electra ;
Diekhans, Mark ;
Kokocinski, Felix ;
Aken, Bronwen L. ;
Barrell, Daniel ;
Zadissa, Amonida ;
Searle, Stephen ;
Barnes, If ;
Bignell, Alexandra ;
Boychenko, Veronika ;
Hunt, Toby ;
Kay, Mike ;
Mukherjee, Gaurab ;
Rajan, Jeena ;
Despacio-Reyes, Gloria ;
Saunders, Gary ;
Steward, Charles ;
Harte, Rachel ;
Lin, Michael ;
Howald, Cedric ;
Tanzer, Andrea ;
Derrien, Thomas ;
Chrast, Jacqueline ;
Walters, Nathalie ;
Balasubramanian, Suganthi ;
Pei, Baikang ;
Tress, Michael ;
Manuel Rodriguez, Jose ;
Ezkurdia, Iakes ;
van Baren, Jeltje ;
Brent, Michael ;
Haussler, David ;
Kellis, Manolis ;
Valencia, Alfonso ;
Reymond, Alexandre ;
Gerstein, Mark ;
Guigo, Roderic ;
Hubbard, Tim J. .
GENOME RESEARCH, 2012, 22 (09) :1760-1774
[7]   The OCT4 pseudogene POU5F1B is amplified and promotes an aggressive phenotype in gastric cancer [J].
Hayashi, H. ;
Arao, T. ;
Togashi, Y. ;
Kato, H. ;
Fujita, Y. ;
De Velasco, M. A. ;
Kimura, H. ;
Matsumoto, K. ;
Tanaka, K. ;
Okamoto, I. ;
Ito, A. ;
Yamada, Y. ;
Nakagawa, K. ;
Nishio, K. .
ONCOGENE, 2015, 34 (02) :199-208
[8]  
Jemal A, 2011, CA-CANCER J CLIN, V61, P134, DOI [10.3322/caac.21492, 10.3322/caac.20115, 10.3322/caac.20107]
[9]   Improving theranostics in pancreatic cancer [J].
King, Jeremy ;
Bouvet, Michael ;
Singh, Gagandeep ;
Williams, John .
JOURNAL OF SURGICAL ONCOLOGY, 2017, 116 (01) :104-113
[10]   Long non-coding RNA IRAIN suppresses apoptosis and promotes proliferation by binding to LSD1 and EZH2 in pancreatic cancer [J].
Lian, Yifan ;
Wang, Juan ;
Feng, Jing ;
Ding, Jie ;
Ma, Zhonghua ;
Li, Juan ;
Peng, Peng ;
De, Wei ;
Wang, Keming .
TUMOR BIOLOGY, 2016, 37 (11) :14929-14937