title: Pseudogene OCT4-pg4 functions as a natural micro RNA sponge to regulate OCT4 expression by competing for miR-145 in hepatocellular carcinoma.
abstract: The POU transcription factor OCT4 is a pleiotropic regulator of gene expression in embryonic stem cells. Recent studies demonstrated that OCT4 is aberrantly expressed in multiple types of human cancer; however, the underlying molecular mechanism remains largely unknown. In this study, we report that OCT4-pg4, a pseudogene of OCT4, is abnormally activated in hepatocellular carcinoma (HCC). The expression level of OCT4-pg4 is positively correlated with that of OCT4, and both gene transcripts can be directly targeted by a tumor-suppressive micro RNA miR-145. We find that the non-coding RNA OCT4-pg4 is biologically active, as it can upregulate OCT4 protein level in HCC. Mechanistic analysis revealed that OCT4-pg4 functions as a natural micro RNA sponge to protect OCT4 transcript from being inhibited by miR-145. In addition, our study also showed that OCT4-pg4 can promote growth and tumorigenicity of HCC cells, thus exerting an oncogenic role in hepatocarcinogenesis. Furthermore, survival analysis suggests that high OCT4-pg4 level is significantly correlated with poor prognosis of HCC patients. Taken together, our finding adds a new layer of post-transcriptional regulation of OCT4 and sheds new light on the treatment of human HCC.
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an, China. rna_research@yahoo.cn
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Zhang-Yan
authors.initials: ZY
authors.lastname: Guo
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Xin
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Wen
authors.forename: Lin-Tao
authors.initials: LT
authors.lastname: Jia
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Yao
authors.forename: An-Gang
authors.initials: AG
authors.lastname: Yang
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis / Q000235:genetics*; D011379:Prognosis; D011544:Pseudogenes; D012323:RNA Processing, Post-Transcriptional; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human