Transcribed pseudogene psi PPM1K generates endogenous siRNA to suppress oncogenic cell growth in hepatocellular carcinoma

Wen-Ling Chan, Chung-Yee Yuo, Wen-Kuang Yang, Shih-Ya Hung, Ya Sian Chang, Chien-Chih Chiu, Kun-Tu Yeh, Hsien-Da Huang, Jan Gowth Chang

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

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.
Original languageEnglish
Pages (from-to)3734-3747
Number of pages14
JournalNucleic Acids Research
Volume41
Issue number6
DOIs
StatePublished - Apr 2013

Keywords

  • EMBRYONIC STEM-CELLS; MESSENGER-RNAS; MICRORNA TARGETS; INTERFERING RNAS; GENE-EXPRESSION; NONCODING RNAS; FLOW-CYTOMETRY; SOMATIC-CELLS; MOUSE OOCYTES; HAIRPIN RNAS

Fingerprint Dive into the research topics of 'Transcribed pseudogene psi PPM1K generates endogenous siRNA to suppress oncogenic cell growth in hepatocellular carcinoma'. Together they form a unique fingerprint.

  • Cite this

    Chan, W-L., Yuo, C-Y., Yang, W-K., Hung, S-Y., Chang, Y. S., Chiu, C-C., Yeh, K-T., Huang, H-D., & Chang, J. G. (2013). Transcribed pseudogene psi PPM1K generates endogenous siRNA to suppress oncogenic cell growth in hepatocellular carcinoma. Nucleic Acids Research, 41(6), 3734-3747. https://doi.org/10.1093/nar/gkt047