標題: Transcribed pseudogene psi PPM1K generates endogenous siRNA to suppress oncogenic cell growth in hepatocellular carcinoma
作者: Chan, Wen-Ling
Yuo, Chung-Yee
Yang, Wen-Kuang
Hung, Shih-Ya
Chang, Ya-Sian
Chiu, Chien-Chih
Yeh, Kun-Tu
Huang, Hsien-Da
Chang, Jan-Gowth
生物科技學系
生物資訊及系統生物研究所
Department of Biological Science and Technology
Institude of Bioinformatics and Systems Biology
公開日期: 1-Apr-2013
摘要: Pseudogenes, especially those that are transcribed, may not be mere genomic fossils, but their biological significance remains unclear. Postulating that in the human genome, as in animal models, pseudogenes may function as gene regulators through generation of endo-siRNAs (esiRNAs), antisense RNAs or RNA decoys, we performed bioinformatic and subsequent experimental tests to explore esiRNA-mediated mechanisms of pseudogene involvement in oncogenesis. A genome-wide survey revealed a partial retrotranscript pseudogene psi PPM1K containing inverted repeats capable of folding into hairpin structures that can be processed into two esiRNAs; these esiRNAs potentially target many cellular genes, including NEK8. In 41 paired surgical specimens, we found significantly reduced expression of two predicted psi PPM1K-specific esiRNAs, and the cognate gene PPM1K, in hepatocellular carcinoma compared with matched non-tumour tissues, whereas the expression of target gene NEK8 was increased in tumours. Additionally, NEK8 and PPM1K were downregulated in stably transfected psi PPM1K-overexpressing cells, but not in cells transfected with an esiRNA1-deletion mutant of psi PPM1K. Furthermore, expression of NEK8 in psi PPM1K-transfected cells demonstrated that NEK8 can counteract the growth inhibitory effects of psi PPM1K. These findings indicate that a transcribed pseudogene can exert tumour-suppressor activity independent of its parental gene by generation of esiRNAs that regulate human cell growth.
URI: http://dx.doi.org/10.1093/nar/gkt047
http://hdl.handle.net/11536/21686
ISSN: 0305-1048
DOI: 10.1093/nar/gkt047
期刊: NUCLEIC ACIDS RESEARCH
Volume: 41
Issue: 6
起始頁: 3734
結束頁: 3747
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