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

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,...

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Bibliographic Details
Published in:Cell research 2012-09, Vol.22 (9), p.1374-1389
Main Authors: Su, Wen-Yu, Li, Jiong-Tang, Cui, Yun, Hong, Jie, Du, Wan, Wang, Ying-Chao, Lin, Yan-Wei, Xiong, Hua, Wang, Ji-Lin, Kong, Xuan, Gao, Qin-Yan, Wei, Li-Ping, Fang, Jing-Yuan
Format: Article
Language:English
Subjects:
3' Untranslated Regions
Adaptor Proteins, Signal Transducing - antagonists & inhibitors
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Cell Line, Tumor
Cell Proliferation
E2F1 Transcription Factor - metabolism
Humans
Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors
Mitogen-Activated Protein Kinase 3 - metabolism
Original
Oxidoreductases Acting on CH-NH Group Donors - antagonists & inhibitors
Oxidoreductases Acting on CH-NH Group Donors - genetics
Oxidoreductases Acting on CH-NH Group Donors - metabolism
RNA Interference
RNA Stability
RNA, Antisense - metabolism
RNA, Messenger - metabolism
RNA, Small Interfering - metabolism
Stomach Neoplasms - genetics
Stomach Neoplasms - metabolism
Stomach Neoplasms - pathology
Up-Regulation
双向调节
反义RNA
基因表达调控
正相关关系
编码蛋白质
胃癌
自然
转录
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Summary: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.
ISSN:1001-0602
1748-7838
DOI:10.1038/cr.2012.57