title: The aberrant expression of MEG3 regulated by UHRF1 predicts the prognosis of hepatocellular carcinoma.
abstract: MEG3 as a tumor suppressor has been reported to be linked with pathogenesis of malignancies including hepatocellular carcinoma (HCC). However, the mechanism of MEG3 in HCC still remains unclear. In our study, the aberrant decreased level of MEG3 in 72 tumor tissues obtained from HCC patients and cell lines was examined by using real-time PCR. The inhibition affection in proliferation and inducing affection in apoptosis was further confirmed in vivo and vitro, we also demonstrated that MEG3 regulates HCC cell proliferation and apoptosis partially via the accumulation of p53. Besides, the hypermethylation of MEG3 in promoter region was identified by bisulfite sequencing while MEG3 increased with the inhibition of methylation. Subsequently, UHRF1, a new identified oncogene which is required for DNA methylation and recruits, was investigated. A negative correlation of MEG3 and UHRF1 expression was verified in primary HCC tissues. Down-regulation of UHRF1 induced MEG3 expression in HCC cell lines, which could be reversed by the up-regulation of UHRF1. In addition, up-regulation of MEG3 in HCC cells partially diminished the promotion of proliferation induced by UHRF1. Moreover, Kaplan-Meier analysis demonstrated that the patients with low expression of MEG3 indicated worse overall and relapse-free survivals compared with high expression of MEG3. Cox proportional hazards analyses showed that MEG3 expression was an independent prognostic factor for HCC patients. In conclusion, we demonstrated MEG3, acting as a potential biomarker in predicting the prognosis of HCC, was regulated by UHRF1 via recruiting DNMT1 and regulated p53 expression.
authors: Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China.
authors: Han
authors: H
authors: Zhuo
authors: Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China.
authors: Junwei
authors: J
authors: Tang
authors: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China.
authors: Zhe
authors: Z
authors: Lin
authors: Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China.
authors: Runqiu
authors: R
authors: Jiang
authors: Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China.
authors: Xudong
authors: X
authors: Zhang
authors: Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China.
authors: Jie
authors: J
authors: Ji
authors: Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China.
authors: Ping
authors: P
authors: Wang
authors: Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China.
authors: Beicheng
authors: B
authors: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D011379:Prognosis; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D044767:Ubiquitin-Protein Ligases
chemical_list: D014408:Biomarkers, Tumor; D022762:CCAAT-Enhancer-Binding Proteins; C498907:MEG3 non-coding RNA, human; D062085:RNA, Long Noncoding; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: biomarker; hypermethylation; long non-coding RNA