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miR-122-mediated translational repression of PEG10 and its suppression in human hepatocellular carcinoma.
- Source :
-
Journal of translational medicine [J Transl Med] 2016 Jul 02; Vol. 14 (1), pp. 200. Date of Electronic Publication: 2016 Jul 02. - Publication Year :
- 2016
-
Abstract
- Background: Hepatocellular carcinoma (HCC), a primary liver malignancy, is the most common cancer in males and fourth common cancer in females in Taiwan. HCC patients usually have a poor prognosis due to late diagnosis. It has been classified as a complex disease because of the heterogeneous phenotypic and genetic traits of the patients and a wide range of risk factors. Micro (mi)RNAs regulate oncogenes and tumor suppressor genes that are known to be dysregulated in HCC. Several studies have found an association between downregulation of miR-122, a liver-specific miRNA, and upregulation of paternally expressed gene 10 (PEG10) in HCC; however, the correlation between low miR-122 and high PEG10 levels still remains to be defined and require more investigations to evaluate their performance as an effective prognostic biomarker for HCC.<br />Methods: An in silico approach was used to isolate PEG10, a potential miR-122 target implicated in HCC development. miR-122S binding sites in the PEG10 promoter were evaluated with a reporter assay. The regulation of PEG10 by miR-122S overexpression was examined by quantitative RT-PCR, western blotting, and immunohistochemistry in miR-122 knockout mice and liver tissue from HCC patients. The relationship between PEG10 expression and clinicopathologic features of HCC patients was also evaluated.<br />Results: miR-122 downregulated the expression of PEG10 protein through binding to 3'-untranslated region (UTR) of the PEG10 transcript. In miR-122 knockout mice and HCC patients, the deficiency of miR-122 was associated with HCC progression. The expression of PEG10 was increased in 57.3 % of HCC as compared to paired non-cancerous tissue samples. However, significant upregulation was detected in 56.5 % of patients and was correlated with Okuda stage (P = 0.05) and histological grade (P = 0.001).<br />Conclusions: miR-122 suppresses PEG10 expression via direct binding to the 3'-UTR of the PEG10 transcript. Therefore, while PEG10 could not be an ideal diagnostic biomarker for HCC but its upregulation in HCC tissue still has predictive value for HCC prognosis.
- Subjects :
- 3' Untranslated Regions genetics
Animals
Apoptosis Regulatory Proteins
Base Sequence
Carcinoma, Hepatocellular pathology
Cell Line, Tumor
DNA-Binding Proteins
Down-Regulation genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Liver Neoplasms pathology
Male
Mice, Knockout
MicroRNAs genetics
Middle Aged
Models, Biological
Neoplasm Grading
Proteins metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
RNA-Binding Proteins
Transcription, Genetic
Up-Regulation genetics
alpha-Fetoproteins metabolism
Carcinoma, Hepatocellular genetics
Liver Neoplasms genetics
MicroRNAs metabolism
Protein Biosynthesis genetics
Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1479-5876
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 27370270
- Full Text :
- https://doi.org/10.1186/s12967-016-0956-z