EpCAM was a potential oncogene and contributed to the growth of gastric cancer. Our data first provided compelling evidence of potential value of EpCAM in the therapy of gastric cancer in clinic.

Osteopontin (OPN), cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are overexpressed in various experimental models of malignancy. However, the correlation and role of the three molecules in gastric cancer is unclear. In the present study, we found that OPN, COX-2 and VEGF were overexpressed in 53 cancerous tissues with gastric cancer compared with 40 normal mucosa tissues by immunohistochemistry method. Moreover, the results indicated co-expression of OPN, COX-2, and VEGF in gastric cancer. Levels of OPN, COX-2, and VEGF were all significantly correlated with TNM stage, lymph node metastasis and distant metastasis (P < 0.05), while not related to prognosis of patients. In addition, individual levels of OPN, COX-2, and VEGF were all significantly correlated with microvessel density (MVD), valued by CD34 staining directly with r-values of 0.416, 0.400, and 0.566, respectively (P < 0.01). Both OPN and COX-2 levels showed a positive correlation with VEGF (P < 0.05). Meanwhile, expression of COX-2 is in relation to OPN (P < 0.01). Overall, survival for patients with high MVD was significantly lower than for patients with low MVD (P < 0.05). Our findings indicate that OPN, COX-2, and VEGF synergically promote angiogenesis and metastasis in gastric cancer. It may be an important and useful strategy to target these molecules for prevention and therapy of tumor.

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Cellular prion protein (PrP(C)), a copper-binding glycosyl-phosphatidylinositol (GPI)-anchored membrane protein that is expressed predominantly in neurons can be induced in ischemia/hypoxic brain tissues. It was also found to be overexpressed and conferred multidrug resistance, promoting cancer metastasis and inhibiting apoptosis in gastric cancer in our lab. In solid tumors, hypoxia can promote malignant progression and confer resistance to chemotherapy by altering gene expression. In present study, we investigated the molecular mechanisms and signaling pathway involved in the induction of the PrP(C) gene by hypoxia in cancer cell lines. PrP(C) was detected to be upregulated in several cancer cell lines at both mRNA and protein level, and then found to be induced by hypoxia in a time-dependent manner. After hypoxia treatment, gastric cancer MKN28 cells transfected with luciferase reporter constructs of the human PrP(C) promoter, which contained HSE, expressed higher luciferase activities (4.3-fold) than those cells transfected with the constructs containing no HSE. In addition, the upregulation of PrP(C) was reduced by MERK/ERK inhibitor (PD98059). siRNA knockdown of PrP(C) could make the cells more sensitive to hypoxia induced drug sensitivity. In conclusion, from these findings, we can propose that some transcriptional factors phosphorylated by ERK1/2, could in turn interact with HSE in the promoter of PrP(C) resulting in upregulation of PrP(C) in gastric cancer cell line MKN28 during hypoxia. Downregulation of PrP(C) makes gastric cancer cells more sensitive to hypoxia induced drug sensitivity. However, other mechanisms might also be responsible for hypoxia induced overexpression of PrP(C) in gastric cancer.

BackgroundThe ZHX family has recently been in the spotlight as an integrator and an indispensable node in carcinogenesis, whose expression is frequently dysregulated in multiple cancers. The current study provides a novel investigation of the expression profiles of ZHX factors in breast cancer.Materials and methodsThe mRNA levels of ZHXs and follow-up periods in breast cancer patients were mined through the Oncomine, Cancer Cell Line Encyclopedia, bc-GenExMiner, cBioPortal and Kaplan–Meier plotter databases. In addition, ZHX3 protein expression was examined in 98 primary tumor samples by immunohistochemistry to investigate its association with clinicopathological parameters and patient outcomes.ResultsWe found that the transcriptional levels of ZHX1, ZHX2 and ZHX3 were not significantly altered in tumor tissues compared with those in nontumor tissues. ZHX2 and ZHX3 mRNA levels were observed to be positively correlated with estrogen receptor and progesterone receptor expression, while ZHX2 mRNA levels were negatively associated with HER2 expression. Survival analyses revealed that high mRNA levels of ZHX2 and ZHX3 correlated with better overall survival in patients with breast cancer. Immunohistochemical analysis revealed that patients with decreased ZHX3 protein levels had poorer outcomes. Multivariate analysis exhibited that ZHX3 expression may serve as an independent high-risk prognostic predictor.ConclusionDysregulated expression of ZHXs may be involved in the progression of breast cancer and could serve as a novel biomarker and potential target for breast cancer.

Osteopontin (OPN) plays an important role in tumorigenesis, tumor invasion, and metastasis in many types of cancers, including gastric cancer. Recently, much interest has been focused on the role of OPN in tumor angiogenesis. Our previous studies have shown that OPN is overexpressed, and associated with mean microvessel density in, the tissue samples of patients with gastric cancer. In the present study, we aimed to further determine and provide evidence for the role of OPN in gastric-cancer-associated angiogenesis by diminishing OPN expression in gastric cancer cells using the small interference RNA method, and then evaluate the effects of OPN on gastric cancer-associated angiogenesis by in vivo and in vitro assays. Our results revealed that reduced OPN production by gastric cancer cells would reduce the proliferation, migration, and tube formation of human umbilical vein endothelial cells, and lead to a lower microvessel density, i.e., angiogenesis, in transplanted tumors of mice. These data confirm the positive role of OPN in gastric-cancer-associated angiogenesis.

MicroRNA-29a (miR-29a) has recently been in the spotlight as a tumor suppressor whose encoding gene is frequently suppressed in cancers. The aim of the present study was to investigate the biological functions and underlying molecular mechanism by which miR-29a-3p suppresses gastric cancer peritoneum metastasis. Cell proliferation, colony-forming, wound healing and Transwell migration assays were performed in the present study. MiR-29a-3p expression was markedly decreased in gastric cancer cell lines with stronger metastatic potential. Silencing miR-29a-3p expression promoted gastric cancer cell proliferation, colony-forming, migration and invasion. By contrast, overexpression of miR-29a-3p inhibited these biological phenotypes. In addition, it was revealed that miR-29a-3p functioned through downregulating hyaluronan synthase 3 expression. Collectively, dysregulated miR-29a-3p expression in gastric cancer cells was associated with malignant properties primarily relevant to migration and metastasis. The results suggest that miR-29a-3p may be a potential therapeutic target for gastric cancer.

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