Interferon (IFN) regulatory factor 8 is encoded by a novel candidate tumor suppressor gene (IRF8), its promotor is frequently methylated in multiple cancers. However, the promoter methylation status, functions and underlying mechanisms of IRF8 in breast cancer remain unclear. We found that IRF8 was downregulated in breast cancer cell lines and primary tumors, compared with normal breast tissues, mainly because of aberrant promoter methylation. However, its expression was not associated with pathological characteristics. Restoration of IRF8 expression suppressed cell proliferation, colony formation, 5-ethynyl-2′-deoxyuridine incorporation, cell migration and invasion, and induced apoptosis and cell cycle arrest in vitro. IRF8 also inhibited xenograft growth in nude mice in vivo. Competition with IRF8 function by IRF8 mutant (K79E) enhanced cell migration and invasion in 4T1 murine cells in vitro. Importantly, IRF8, as both downstream target gene and regulator of IFN-γ/STAT1 signaling, inhibited canonical β-catenin signaling. These findings identify IRF8 as a novel tumor suppressor regulating IFN-γ/STAT1 signaling and β-catenin signaling in breast cancer.

BackgroundPrevious research found that ALG3 is associated with cervical cancer, but the role of ALG3 in breast cancer was still unknown.Material/MethodsThe expression of ALG3 in breast carcinoma tissues was determined by immunochemistry. The ability of cellular proliferation, migration, and invasion was determined by CCK-8 assay, wound healing migration assay, and cell invasion assays, respectively. The binding between HSF2 and promoter of ALG3 was determined by ChIP assay.ResultsThere was an increased expression of ALG3 in breast cancer tissues compared to normal breast tissues (p<0.05). High expression of ALG3 was significantly correlated with poor OS (p<0.05). ALG3 expression was significantly increased in cancer samples with advanced stages (stage III/IV) compared with those in the early stages of disease (stage I/II) (p<0.05). The staining intensity of ALG3 was significantly correlated to the tumor grade (grades 2–3 versus 1, p<0.05). Silencing ALG3 or HSF2 inhibited the proliferation, migration, and invasion abilities of MCF-7 cells. Silencing ALG3 retarded the growth of MCF-7 cells in vivo.ConclusionsSilencing ALG3 inhibited MCF-7 cells growth in vitro and in vivo. HSF2 activated ALG3 and promoted the growth of breast carcinoma.

To explore the risk factors of ocular metastasis (OM) in patients with hepatocellular carcinoma (HCC) by analyzing the demographic characteristics and serum markers. Methods: From July 2002 to December 2012, 1064 HCC patients were included in our study. The chi-squared test and Student's t-test were used to assess the difference between OM and any other metastasis (NOM). Receiver operating curve (ROC) was used to analyze the diagnostic value of serum biomarkers in HCC patients with OM. Results: The incidence of OM in HCC patients was 1.88% in our research. There are no significant differences in age, gender, or histopathology in the OM group and the group without any metastasis. Binary logistic regression analysis presented that compared with the patients without cancer metastasis, carbohydrate antigen 125 (CA-125) and hemoglobin (Hb) were risk factors in hepatocellular carcinoma patients with OM (P < 0.05). The ROC curve analysis showed that the areas under the CA-125, Hb, and CA125+Hb curves were 0.877, 0.554, and 0.431, and the cutoff values of CA-125 and Hb each were 115.78 u/mL and 120.50 g/L. Conclusion: Our data suggest that CA-125 and Hb are risk indicators in hepatocellular carcinoma patients with OM, and that CA-125 +Hb has potentially greater utility in diagnosing hepatocellular carcinoma.

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