Bidirectional regulation between WDR83 and its natural antisense transcript DHPS in gastric cancer
Bidirectional regulation between WDR83 and its natural antisense transcript DHPS in gastric cancer
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WDR83 及其天然反义转录物 DHP 在胃癌中的双向调控
DOI：
10.1038/cr.2012.57
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发表时间：
2012-09-01
期刊：
影响因子：
44.1
通讯作者：
Fang, Jing-Yuan
中科院分区：
文献类型：
--
作者：
Su, Wen-Yu;Li, Jiong-Tang;Fang, Jing-Yuan
天然反义转录物（NAT）广泛存在于哺乳动物基因组中，在基因表达调控中发挥重要作用。然而，双向反义RNA调控的存在和蛋白质编码基因作为反义RNA发挥功能的可能性仍然是推测性的。在此，我们发现，蛋白编码基因，脱氧羟腐胺赖氨酸合成酶（DHPS），作为NAT的WDR 83，一致地调节WDR 83的mRNA和蛋白质的表达。相反，WDR 83也以一致的方式通过反义配对调节DHPS。WDR 83与DHPS在3′端非翻译区重叠处形成双链体，增加了相互间的稳定性，这是双向调控所必需的。WDR 83和DHPS作为一对编码蛋白质的顺/反义转录本，在胃癌（GC）中同时上调并呈正相关，通过促进细胞增殖驱动GC病理生理。此外，在其他癌症中也观察到WDR 83与DHPS之间的正相关性。WDR 83和DHPS之间的双向调控关系不仅丰富了我们对反义调控的理解，而且还提供了对它们在肿瘤发展中的功能的更完整的理解。
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.