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Pseudogene OCT4-pg4 functions as a natural micro RNA sponge to regulate OCT4 expression by competing for miR-145 in hepatocellular carcinoma
- Source :
- Carcinogenesis. 34:1773-1781
- Publication Year :
- 2013
- Publisher :
- Oxford University Press (OUP), 2013.
-
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.
- Subjects :
- Cancer Research
Carcinoma, Hepatocellular
Transcription, Genetic
Carcinogenesis
cells
Pseudogene
Mice, Nude
Biology
Bioinformatics
Mice
Transcription (biology)
Cell Line, Tumor
microRNA
Gene expression
Animals
Humans
RNA Processing, Post-Transcriptional
Gene
Transcription factor
reproductive and urinary physiology
Cell Proliferation
Mice, Inbred BALB C
Liver Neoplasms
fungi
HEK 293 cells
RNA
Hep G2 Cells
General Medicine
Prognosis
Up-Regulation
MicroRNAs
HEK293 Cells
embryonic structures
Cancer research
biological phenomena, cell phenomena, and immunity
Octamer Transcription Factor-3
Pseudogenes
Subjects
Details
- ISSN :
- 14602180 and 01433334
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Carcinogenesis
- Accession number :
- edsair.doi.dedup.....ae77d0741780b7a8ad53dc47c70aabd3