miR-122-mediated translational repression of PEG10 and its suppression in human hepatocellular carcinoma

Journal of Translational Medicine

Research

Ji-Fan Lin¹  Mu-Jie Lu²  Chia-Wen Hsieh²  Rong-Nan Chien³  Ting-Shuo Huang⁴  Yu-Chiau Shyu⁵  Tung-Liang Lee⁶  Huang-Yang Chen⁷  Yu-Hsien Chen⁷  Jim-Ray Chen⁸  Ann-Ping Tsou⁹ 

[1] Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan;Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan;Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan;Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital and University, Keelung 204, Taiwan;Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan;Department of General Surgery, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan;Department of Chinese Medicine, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 259, Taiwan;Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan;Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan;Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA;Department of General Surgery, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan;Department of Pathology, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan;Department of Medicine, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 259, Taiwan;Institute of Biotechnology in Medicine, National Yang Ming University, Taipei 112, Taiwan;

关键词: miR122;    PEG10;    HCC;   

DOI  :  10.1186/s12967-016-0956-z

 received in 2016-01-24, accepted in 2016-06-22,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundHepatocellular 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.MethodsAn 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.ResultsmiR-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).ConclusionsmiR-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.

【 授权许可】

CC BY   
© The Author(s) 2016