The receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) is a transmembrane protein belongs to receptor tyrosine kinase (RTK) family. This study aimed to examine the expression of ROR1 in human ovarian cancer and investigate the relationship between its expression and the prognosis of ovarian cancer patients. In this present study, one-step quantitative reverse transcription-polymerase chain reaction (15 ovarian cancer samples of high FIGO stage, 15 ovarian cancer samples of low FIGO stage and nine normal ovary tissue samples) and immunohistochemistry by tissue microarrays (100 ovarian cancer samples and 50 normal ovary samples) were performed to characterize expression of the ROR1 gene in ovarian cancer. Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of ovarian cancer. The results of qPCR and IHC analysis showed that the expression of ROR1 in ovarian cancer was significantly higher than that in normal ovary tissues (all p < 0.05). Survival analysis showed that ROR1 protein expression was one of the independent prognostic factors for disease-free survival and overall survival (both p < 0.05). The data suggest that ROR1 expression is correlated with malignant attributes of ovarian cancer and it may serve as a novel prognostic marker in ovarian cancer.

miRNAs play important roles in lung adenocarcioma (LADC) progression. We previously found that miR-1290 expression was upregulated in LADC tissue and serum samples from patients with LADC, and correlated with prognosis. However, the biological role of miR-1290 in LADC and mechanism of such role are poorly understood. Here, we found that miR-1290 overexpression promoted LADC cell proliferation, cell cycle progression and invasion, while suppressing cell apoptosis in vitro. Furthermore, miR-1290 promoted tumor growth, invasion and metastasis in vivo. miR-1290 downregulated suppressor of cytokine signaling 4 (SOCS4) at both the mRNA and protein levels by targeting SOCS4. Reduced SOCS4 level reversed the inhibitory effect of miR-1290 downregulation on cell proliferation and invasion. miR-1290 activated the JAK/STAT3 and PI3K/AKT signaling pathways by targeting SOCS4. An inverse correlation was observed between miR-1290 and SOCS4 expression in LADC tissues. Clinicopathological characteristics analysis showed that SOCS4 expression was negatively associated with higher clinical stage and lymph node metastasis. These observations suggest that miR-1290 promotes LADC cell proliferation and invasion by targeting SOCS4.

No abstract

MiR-145 could inhibit invasion and migration of lung adenocarcinoma cell lines by directly targeting N-cadherin.

Data regarding the association between surgical margin status and the outcome of bladder cancer treated by radical cystectomy (RC) are conflicting. Therefore, the present meta-analysis was performed to assess the associations between the outcomes of bladder cancer, in terms of recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS), and the presence of positive surgical margins versus negative surgical margins following treatment with RC. Research articles published prior to April 2016 were identified from Pubmed, Embase and the Cochrane Library databases. A total of 36 articles were included, with a sample size of 38,384 bladder cancer patients. Of these, 4,354 patients were reported to have positive surgical margins. Significant associations were detected between positive surgical margins following RC and unfavorable RFS [summary relative risk estimate (SRRE), 1.63; 95% confidence interval (CI), 1.46-1.83; P = 0.105], CSS (SRRE, 1.82; 95% CI, 1.63-2.04; P = 0.001) and OS (SRRE, 1.68; 95% CI, 1.58-1.80; P = 0.805), by fixed or random effects models. The findings were consistent independently of age, sample size, publication year, follow-up duration, study type and geographical region. In summary, the present findings demonstrate that the presence of positive surgical margins is associated with poor survival outcomes in bladder cancer following RC, indicating that avoidance of positive surgical margins during surgery is helpful to improve the prognosis of patients with bladder cancer.

Background/Aims: GLP-1 and ghrelin are common appetite-regulating hormones. Both have multiple functions beyond metabolic regulation. However, the effects of GLP-1 and ghrelin on endothelial biology are not fully understood. Here, we investigate the roles of GLP-1 and ghrelin in microvascular endothelial apoptosis and senescence. Methods: Human microvascular endothelial cells (HMECs) were exposed to high glucose/high lipid (HG/HL) conditions and treated with GLP-1 or ghrelin. Cellular apoptosis, senescence, and mitochondrial function were measured. In addition, the MAPK and Akt signaling pathways were examined. Results: Both GLP-1 and ghrelin treatment decreased the number of TUNEL-positive cells and inhibited caspase-3 and PARP cleavage and mitochondrial dysfunction in HG/HL-exposed HMECs. GLP-1, but not ghrelin decreased the number of β-galactosidase (β-gal)-positive cells. Furthermore, GLP-1 and ghrelin inhibited ERK1/2, JNK1/2, and p38 signaling. GLP-1 suppressed Akt signaling, but ghrelin had no effect. Moreover, JNK1/2 and p38 inhibitors, but not ERK1/2 and Akt inhibitors, decreased the number of TUNEL-positive cells. Additionally, only the Akt inhibitor decreased the number of β-gal-positive cells. Conclusion: These results demonstrate that GLP-1 and ghrelin inhibit mitochondrial dysfunction under HG/HL conditions, and suppress endothelial apoptosis via inhibiting JNK1/2 and p38 signaling; moreover, GLP-1 alleviates endothelial senescence via inactivating Akt signaling.

BackgroundThis study aimed to investigate the effect of deferoxamine (DFO) on leukemia in vitro, and to explore the underlying molecular mechanism.Material/MethodsK562 leukemia cells were treated with various concentrations of DFO (10, 50, and 100 μmol/l) with or without 10 μmol/l ferric chloride for 12 h. Then, total cellular iron was detected. CCK-8 kit and flow cytometry were used for cell viability and apoptosis detection. In addition, expression of apoptosis-related genes was determined by Western blotting and qRT-PCR, respectively.ResultsThe results suggested that DFO significantly inhibited K562 cell viability and induced cell apoptosis in a dose-dependent manner. We also found that the protein and mRNA levels of Bax, p53, and Fas dose-dependently increased in DFO-treated K562 cells, while the level of Bcl-2 markedly decreased in a dose-dependent manner. Moreover, the findings showed that ferric chloride eliminated these effects on K562 cells caused by DFO treatment.ConclusionsOur results indicate that DFO plays a protective role in leukemia via inhibiting leukemia cell viability and inducing cell apoptosis by the regulation of apoptosis-related genes expression.

Th2 cytokine expression is dependent on the transcription factor GATA-3. However, the molecular interactions of GATA-3 leading to Th2 cytokine gene activation have not been well characterized. Here, we reported a number of GATA-3 associated proteins in Th2 cells, and one of such proteins Pias1 functioned as a positive transcriptional coregulator for GATA-3. When overexpressed in Th2 cells, Pias1 enhanced the expression of IL-13, and to lesser degrees, IL-4 and -5. Conversely, Pias1 siRNA down-regulated the Th2 cytokine expression. In Leishmania major infection, manipulating Pias1 expression in parasite-reactive CD4 T cells altered severity of disease caused by Th2 responses. Mechanistically, Pias1 markedly potentiated GATA-3-mediated activation of the IL-13 promoter by facilitating the recruitment of GATA-3 to the promoter. In contrast, IL-5 promoter was modestly enhanced by Pias1 and no effect was observed on IL-4 promoter. Thus, both promoter activation and additional mechanisms are responsible for regulation by Pias1.