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

作　　者：Wen-Yu Su Jiong-Tang Li Yun Cui Jie Hong Wan Du Ying-Chao Wang Yan-Wei Lin Hua Xiong Ji-Lin Wang Xuan Kong Qin-Yan Gao Li-Ping Wei Jing-Yuan Fang 

机构地区：[1]GI Division,Shanghai Jiao-Tong University School of Medicine Renji Hospital,Shanghai Institution of Digestive Disease,Key Laboratory of Gastroenterology&Hepatology,Ministry of Health(Shanghai Jiao-Tong University),State Key Laboratory of Oncogene and Related Genes,145 Middle Shandong Rd,Shanghai 200001,China [2]Chinese Academy of Fishery Science,Ministry of Agriculture,150 Qingta,Yongding Rd,Beijing 100141,China [3]Center for Bioinformatics,National Laboratory of Protein Engineering and Plant Genetic Engineering,College of Life Sciences,Peking University,5 Yiheyuan Rd,Beijing 100871,China

出　　处：《Cell Research》2012年第9期1374-1389,共16页细胞研究（英文版）

基　　金：We are grateful to Dr Tim （Qing-Rong） Liu （National Institutes of Health, USA） for insightful suggestions. We thank the ENCODE Consortium, including the University of Washington ENCODE group, the transcriptome group at Affymetrix, and Cold Spring Harbor Laboratories, for providing the open-accessible transcriptome data and the labs of Michael Snyder, Mark Gerstein, and Sherman Weissman at Yale University and Peggy Farnham at University of California, Davis. This work was supported by grants from the National Basic Research Program of China （973 program; 2010CB5293 to JYF and 2007CB946904 to LPW）, the National Natural Science Foundation of China （30971330 to JYF; National Outstanding Young Investigator Award （31025014） to LPW）, the China Ministry of Science and Technology （863 Hi-Tech R＆D Program; 2007AA02ZI65 to LPW）, and the Doctor Innovation Foundation of Shanghai Jiao-Tong University School of Medicine （BXJ201117 to WYS）.

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 proteincoding 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 patbophysiology 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.

关 键 词：bidirectional regulation natural antisense transcript gastric cancer 

分 类 号：Q522[生物学—生物化学] TN919.81[电子电信—通信与信息系统]