Bidirectional regulation between WDR83 and its natural antisense transcript DHPS in gastric cancer

被引:59
作者
Su, Wen-Yu [1 ,2 ,3 ]
Li, Jiong-Tang [4 ,5 ]
Cui, Yun [1 ,2 ,3 ]
Hong, Jie [1 ,2 ,3 ]
Du, Wan [1 ,2 ,3 ]
Wang, Ying-Chao [1 ,2 ,3 ]
Lin, Yan-Wei [1 ,2 ,3 ]
Xiong, Hua [1 ,2 ,3 ]
Wang, Ji-Lin [1 ,2 ,3 ]
Kong, Xuan [1 ,2 ,3 ]
Gao, Qin-Yan [1 ,2 ,3 ]
Wei, Li-Ping [5 ]
Fang, Jing-Yuan [1 ,2 ,3 ]
机构
[1] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, GI Div,Shanghai Inst Digest Dis, Shanghai 200001, Peoples R China
[2] Shanghai Jiao Tong Univ, Minist Hlth, Key Lab Gastroenterol & Hepatol, Shanghai 200001, Peoples R China
[3] State Key Lab Oncogene & Related Genes, Shanghai 200001, Peoples R China
[4] Chinese Acad Fishery Sci, Minist Agr, Beijing 100141, Peoples R China
[5] Peking Univ, Coll Life Sci, Natl Lab Prot Engn & Plant Genet Engn, Ctr Bioinformat, Beijing 100871, Peoples R China
基金
中国国家自然科学基金;
关键词
bidirectional regulation; natural antisense transcript; gastric cancer; DEOXYHYPUSINE SYNTHASE CDNA; MESSENGER-RNA; GENE-EXPRESSION; ERK ACTIVATION; S-PHASE; PATHWAY; OVEREXPRESSION; TUMORIGENESIS; DEGRADATION; INHIBITION;
D O I
10.1038/cr.2012.57
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Natural antisense transcripts (NATs) exist ubiquitously in mammalian genomes and play roles in the regulation of gene expression. However, both the existence of bidirectional antisense RNA regulation and the possibility of protein-coding genes that function as antisense RNAs remain speculative. Here, we found that the protein-coding gene, deoxyhypusine synthase (DHPS), as the NAT of WDR83, concordantly regulated the expression of WDR83 mRNA and protein. Conversely, WDR83 also regulated DHPS by antisense pairing in a concordant manner. WDR83 and DHPS were capable of forming an RNA duplex at overlapping 3' untranslated regions and this duplex increased their mutual stability, which was required for the bidirectional regulation. As a pair of protein-coding cis-sense/antisense transcripts, WDR83 and DHPS were upregulated simultaneously and correlated positively in gastric cancer (GC), driving GC pathophysiology by promoting cell proliferation. Furthermore, the positive relationship between WDR83 and DHPS was also observed in other cancers. The bidirectional regulatory relationship between WDR83 and DHPS not only enriches our understanding of antisense regulation, but also provides a more complete understanding of their functions in tumor development.
引用
收藏
页码:1374 / 1389
页数:16
相关论文
共 49 条
[1]
Antisense transcription: A critical look in both directions [J].
Beiter, T. ;
Reich, E. ;
Williams, R. W. ;
Simon, P. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2009, 66 (01) :94-112
[2]
The ets-related transcription factor GABP directs bidirectional transcription [J].
Collins, Patrick J. ;
Kobayashi, Yuya ;
Nguyen, Loan ;
Trinklein, Nathan D. ;
Myers, Richard M. .
PLOS GENETICS, 2007, 3 (11) :2247-2255
[3]
Spatially separate docking sites on ERK2 regulate distinct signaling events in vivo [J].
Dimitri, CA ;
Dowdle, W ;
MacKeigan, JP ;
Blenis, J ;
Murphy, LO .
CURRENT BIOLOGY, 2005, 15 (14) :1319-1324
[4]
Complex loci in human and mouse genomes [J].
Engstrom, Par G. ;
Suzuki, Harukazu ;
Ninomiya, Noriko ;
Akalin, Altuna ;
Sessa, Luca ;
Lavorgna, Giovanni ;
Brozzi, Alessandro ;
Luzi, Lucilla ;
Tan, Sin Lam ;
Yang, Liang ;
Kunarso, Galih ;
ng, Edwin Lian-Cho Ng ;
Batalov, Serge ;
Wahlestedt, Claes ;
Kai, Chikatoshi ;
Kawai, Jun ;
Carninci, Piero ;
Hayashizaki, Yoshihide ;
Wells, Christine ;
Bajic, Vladimir B. ;
Orlando, Valerio ;
Reid, James F. ;
Lenhard, Boris ;
Lipovich, Leonard .
PLOS GENETICS, 2006, 2 (04) :564-577
[5]
Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of β-secretase [J].
Faghihi, Mohammad Ali ;
Modarresi, Farzaneh ;
Khalil, Ahmad M. ;
Wood, Douglas E. ;
Sahagan, Barbara G. ;
Morgan, Todd E. ;
Finch, Caleb E. ;
Laurent, Georges St., III ;
Kenny, Paul J. ;
Wahlestedt, Claes .
NATURE MEDICINE, 2008, 14 (07) :723-730
[6]
Evidence for natural antisense transcript-mediated inhibition of microRNA function [J].
Faghihi, Mohammad Ali ;
Zhang, Ming ;
Huang, Jia ;
Modarresi, Farzaneh ;
Van der Brug, Marcel P. ;
Nalls, Michael A. ;
Cookson, Mark R. ;
St-Laurent, Georges, III ;
Wahlestedt, Claes .
GENOME BIOLOGY, 2010, 11 (05)
[7]
Regulatory roles of natural antisense transcripts [J].
Faghihi, Mohammad Ali ;
Wahlestedt, Claes .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (09) :637-643
[8]
The highways and byways of mRNA decay [J].
Garneau, Nicole L. ;
Wilusz, Jeffrey ;
Wilusz, Carol J. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2007, 8 (02) :113-126
[9]
miRBase: microRNA sequences, targets and gene nomenclature [J].
Griffiths-Jones, Sam ;
Grocock, Russell J. ;
van Dongen, Stijn ;
Bateman, Alex ;
Enright, Anton J. .
NUCLEIC ACIDS RESEARCH, 2006, 34 :D140-D144
[10]
Reduced Morg1 expression in ischemic human brain [J].
Haase, Daniela ;
Keiner, Silke ;
Mawrin, Christian ;
Wolf, Gunter .
NEUROSCIENCE LETTERS, 2009, 455 (01) :46-50