EZH2 promotes metabolic reprogramming in glioblastomas through epigenetic repression of EAF2-HIF1α signaling.

Cancer cells prefer glycolysis for energy metabolism, even when there is sufficient oxygen to make it unnecessary. This is called the Warburg effect, and it promotes tumorigenesis and malignant progression. In this study, we demonstrated that EZH2, a multifaceted oncogenic protein involved in tumor proliferation, invasion and metastasis, promotes glioblastoma tumorigenesis and malignant progression through activation of the Warburg effect. We observed that HIF1α is a target of EZH2 whose activation is necessary for EZH2-mediated metabolic adaption, and that HIF1α is activated upon EZH2 overexpression. EZH2 suppressed expression of EAF2, which in turn upregulated HIF1α levels. We conclude from these results that EZH2 promotes tumorigenesis and malignant progression in part by activating glycolysis through an EAF2-HIF1α signaling axis.

The overexpression of epithelial cell adhesion molecule (EpCAM) in glioma.

Epithelial cell adhesion molecule (EpCAM) is overexpressed in various neoplasms as a tumor-associated antigen and absent in natural brain. However, little is known about EpCAM's expression in gliomas. To investigate the expression of EpCAM in gliomas and understand the correlation of EpCAM expression with malignancy, proliferation, angiogenesis, and prognosis, we studied the expression of EpCAM in 98 glioma samples by immunohistochemistry and by western blotting (N = 12). Correlative analysis of EpCAM overexpression with microvessel density (MVD), Ki-67 expression, age, and gender were made. Survival data was analyzed with Kaplan-Meier method and Cox Proportional Hazard Model. Immunohistochemistry results showed EpCAM was widely expressed in glioma (90.8 %). The overexpression rate of WHO grade IV gliomas was significantly higher EpCAM overexpression correlated significantly with Ki-67 expression and MVD. Western blot analysis also revealed a stepwise increase in EpCAM expression from WHO II to IV glioma. The overall survival of WHO III and IV glioma patients with EpCAM overexpression was obviously lower than that without EpCAM overexpression. EpCAM overexpression was an independent prognostic factor for overall survival in glioma patients. This study firstly shows that EpCAM overexpression correlates significantly with malignancy (WHO grades), proliferation (Ki67), angiogenesis (MVD), and prognosis in gliomas. EpCAM may participate in tumorgenesis of gliomas.

Recurrent miscarriage is associated with a decline of decidual natural killer cells expressing killer cell immunoglobulin-like receptors specific for human leukocyte antigen C.

AIM: To investigate the relationship between natural killer (NK) cell phenotype and recurrent miscarriage (RM). METHODS: We studied killer cell immunoglobulin-like receptor (KIR) expression on decidual NK cells in women with RM. RESULTS: The expression of KIR2DL1/S1 on CD56(+) CD16(-) NK cells in the deciduas of these women was significantly lower than in that of control subjects (P = 0.026). There was a significant decline in the frequency of CD56(+) CD16(-) NK cells staining for KIR2DL1/S1 and KIR2DL2/S2/L3 throughout the first trimester in patients (P < 0.05). Furthermore, by stratification of the women in three groups according to gestational stage, it was found that KIR2DL1/S1 expressing NK cells were significantly decreased in all groups, especially around gestational days 50-70 (P = 0.010). CONCLUSION: This is the first report to demonstrate that RM is associated with a decline in the frequency of decidual NK cells expressing KIR specific for human leukocyte antigen (HLA)-C, and in which gestational stage was considered. The results suggest that KIR phenotype contributes to the pathogenesis of the disease, and that assessment of KIR may serve as a diagnostic tool.

Inhibitory effect of 2'-o-methoxyethyl-modified antisense oligonucleotides targeting vascular endothelial growth factor A on SKOV3 human ovarian cancer cells.

BACKGROUND: Ovarian cancers are often at an advanced stage at diagnosis because early detection is difficult. The poor prognosis of ovarian cancers highlights the crucial need to develop better therapeutic agents and strategies. The objective of this study was to investigate the inhibitory effects of a new modified antisense oligonucleotides targeting vascular endothelial growth factor A (VEGF-A) in SKOV3 ovarian cancer cells. METHODS: Antisense oligonucleotides targeting VEGF-A was designed, synthesized and transfected into SKOV3 ovarian cancer cells. Western blotting and real-time RT-PCR were used to analyze the inhibitory effects of antisense oligonucleotides on VEGF-A protein and mRNA expression. Transwell matrix assay was used to detect cell migration inhibition. RESULTS: The antisense oligonucleotides targeting VEGF-A significantly decreased VEGF-A protein and mRNA expression and inhibited cell migration in SKOV3 ovarian cancer cells. CONCLUSIONS: This new modified antisense oligonucleotides targeting VEGF-A can decrease VEGF-A expression and inhibit cell migration in SKOV3 ovarian cancer cells. This new oligonucleotides may be a promising therapeutic agent for ovarian cancers.