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Although the abnormal expression of Polycomb-group (PcG) proteins is closely associated with carcinogenesis and the clinicopathological features of hepatocellular carcinoma (HCC), the genetic mutation profile of PcG genes has not been well established. In this study of human HCC specimens, we firstly discovered a highly conserved mutation site, G553C, in the Polycomb Repressive Complex 2 (PRC2) gene enhancer of zeste homolog 2 (EZH2). This site also harbors a single nucleotide polymorphism (SNP), rs2302427, which plays an important antagonistic role in HCC. Kaplan-Meier survival curves showed that the tumor-free and overall survival of patients with EZH2 G553C were superior to those without the mutation. The G allele frequencies in patients and healthy subjects were 0.2% and 0.122%, respectively, with significant differences in distribution. The individuals carrying the GG and the GC genotypes at rs2302427 showed 3.083-fold and 1.827-fold higher risks of HCC, respectively, compared with individuals carrying the wild-type allele. Furthermore, Immunohistochemical staining revealed that the expression levels of CBX8 (in 53/123 samples) and BMI1 (in 60/130 samples) were markedly increased in human HCC specimens. Importantly, the overall and tumor-free survival rates were significantly reduced in the group of patients who simultaneously expressed PRC1 and PRC2. These results argue that a combination of PRC1 and PRC2 expression has a significant predictive/prognostic value for HCC patients. Taken together, our results indicate the abnormal expression and genetic mutation of PcG members are two independent events; cumulative genetic and epigenetic alterations act synergistically in liver carcinogenesis.

Background: Patients with schizophrenia have an increased prevalence of type 2 diabetes mellitus, and type 2 diabetes mellitus has shown an association with the rs4402960 gene polymorphism in the insulin-like growth factor II messenger RNA (mRNA)-binding protein 2 gene (IGF2BP2). We tested this polymorphism and mRNA expression levels of IGF2BP2 for an association in Han Chinese patients with schizophrenia compared to healthy controls., Method: The rs4402960 polymorphism was genotyped in 790 chronic schizophrenic patients (diagnosed according to DSM-IV) and 1,083 unrelated healthy controls in a case-control design. The IGF2BP2 gene expression levels were assayed in 34 patients with chronic schizophrenia and 30 healthy controls by using real-time polymerase chain reaction (PCR). The study was conducted between 2005 and 2007., Results: We found significant differences in the rs4402960 genotype (χ(2)2 = 7.316, P = .026) and allele (χ(2)1 = 7.056, P = .008) distributions between the patient and control groups. The rs4402960 T allelic frequency was significantly higher in male schizophrenic patients than male controls (28.9% vs 23.5%; P = .004) but not in female patients compared to female controls (27.1% vs 25.5%; P = .498). When real-time PCR was used, the IGF2BP2 gene's isoform B expression levels were significantly greater in schizophrenia than controls (P = .0008)., Conclusions: These results suggest that the IGF2BP2 gene may play a role in susceptibility to schizophrenia, supporting the hypothesis that the co-occurrence of type 2 diabetes mellitus and schizophrenia may be explained by shared genetic risk variants. However, this finding remains preliminary since this association has yet to be replicated., (© Copyright 2013 Physicians Postgraduate Press, Inc.)

Objective: To investigate the effect of X-rays on expression of caspase-3 and p53 protein in EL-4 cells and its implications in induction of apoptosis and polyploid cells., Methods: Mouse lymphoma cell line (EL-4 cells) was used. Fluorescent staining and flow cytometry analysis were employed for measurement of protein expression, apoptosis, cell cycle, and polyploid cells., Results: The expression of caspase-3 protein increased significantly at 8 h and 12 h, compared with that of sham-irradiated control (P<0.05, respectively) and the expression of p53 protein increased significantly at 2, 4, 8, 12, and 24 h, compared with that of sham-irradiated control (P<0.05-P<0.01) in EL-4 cells after 4.0 Gy X-irradiation. Apoptosis of EL-4 cells was increased significantly at 2, 4, 8, 12, 24, 48, and 72 h after 4.0 Gy exposure, compared with that of sham-irradiated control (P<0.05-P<0.001). G2 phase cells were increased significantly at 4, 8, 12, 24, 48, and 72 h (P<0.05-P<0.001). However, no marked change in the number of 8 C polyploid cells was found from 2 to 48 h after 4.0 Gy exposure., Conclusion: The expressions of caspase-3 and p53 protein in EL-4 cells are induced by X-rays, which might play an important role in the induction of apoptosis, and the molecular pathway for polyploid formation might be p53-independent.