BackgroundThe aberrant expression of microRNA-140-5p (miR-140-5p) has been described in gastric cancer (GC). However, the role of miR-140-5p in GC remains unclear. In this study, the prognostic relevance of miR-140-5p in GC was investigated and YES1 was identified as a novel target of miR-140-5p in regulating tumor progression.MethodsmiR-140-5p level was determined in 20 paired frozen specimens through quantitative real-time PCR, and analyzed in tissue microarrays through in situ hybridization. The target of miR-140-5p was verified through a dual luciferase reporter assay, and the effects of miR-140-5p on phenotypic changes in GC cells were investigated in vitro and in vivo.ResultsCompared with that in adjacent normal tissues, miR-140-5p expression decreased in cancerous tissues. The downregulated miR-140-5p in 144 patients with GC was significantly correlated with the reduced overall survival of these patients. miR-140-5p could inhibit GC cell proliferation, migration and invasion by directly targeting 3′–untranlated region of YES1. miR-140-5p could also remarkably reduce the tumor size in GC xenograft mice.ConclusionsmiR-140-5p serves as a potential prognostic factor in patients with GC, and miR-140-5p mediated YES1 inhibition is a novel mechanism behind the suppressive effects of miR-140-5p in GC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0708-6) contains supplementary material, which is available to authorized users.
BackgroundThrombospondins (THBSs) are a family of multidomain and secreted matricellular Ca2+-binding glycoproteins which has at least five members encoded by independent genes. As a THBSs family member, Thrombospondin2 (THBS2) has been reported to regulate angiogenesis. Nevertheless, the functions and clinical significance of THBS2 still remains unclear in gastric cancer.MethodsThe mRNA and protein expression levels of THBS2 were assessed in 14 paired of gastric cancer specimens and corresponding normal mucosas using quantitative real-time PCR and western blot analysis. Immunohistochemistry of THBS2 and CD34 on population-based tissue microarrays consisting of 129 gastric cancer cases were used to evaluate the prognostic significance of THBS2 and microvessel density (MVD) of each sample. Survival analyses were performed by Kaplan–Meier method and Cox’s proportional hazards model. Colony formation assay, endothelial cell tube formation assay, cell migration assay and apoptosis analysis in MKN-45 and SGC-7901 cell lines were carried out to evaluate the effects of THBS2 on gastric cancer in vitro.Results85.71% (12 of 14) gastric cancer tissues expressed remarkably lower THBS2 in both mRNA and protein levels than the corresponding normal controls. Consistently, tissue microarray (TMA) results showed THBS2 levels were also inhibited in gastric cancer tissues compared with the normal controls. Moreover, we observed that patients with higher levels of THBS2 were significantly correlated with more favourable prognosis while decreased THBS2 expression were associated with poorer histological grades of gastric cancer. Additionally, our in vitro experiments further demonstrated that overexpression of THBS2 could impede both the proliferation rate and the tube formation of Human umbilical vein endothelial cells (HUVECs) in MKN-45 and SGC-7901 cell lines.ConclusionOur study suggests THBS2 is aberrantly expressed in gastric cancer and plays a critical role in cancer progression, which can be a potential prognosis predictor of gastric cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-13-225) contains supplementary material, which is available to authorized users.
Background The psychological health (PH) of doctors affects the quality of medical service and is related to the safety of patients. The serious problems with the doctor-patient relationship in China can lead to long-term imbalances in doctor PH, and the poor PH status of doctors has raised scholars' concern. Current research mainly focuses on how factors such as social support and the impact of the residential environment correlate with individual PH. We continue this direction of research to see how the mechanism of social support impacts physician PH, also investigating the moderating effect of demographic indicators on physician PH. Methods Based on a survey of 399 physicians, a descriptive analysis of measured data was done using SPSS 19.0. Pearson correlation coefficient analysis was used to examine the correlations between PH and the social support rating scale (SSRS) and the demographic variables. KMO and Bartlett methods were used to examine the correlations between PH and SDS (a scale to measure depression) and between PH and SAS (a scale to measure anxiety). The method of factor analysis was used for multicollinearity tests, and multiple stepwise regression analysis was used to explore the demographic factors correlated with PH and SSRS. Two-way interactions in moderated multiple regression were used to test the moderating effect of education level and title on SSRS, SDS, and SAS. Results Our results indicate that the level of PH is influenced by the age, education, and title of a doctor. A physician's title is significantly and positively correlated with PH, but age and
Gastric cancer is now the fourth most common malignancy and the second leading cause of death because of cancer. The resistance to anticancer drugs is the main cause of chemotherapy failure. In this study, we explored the role of Notch 1 and long noncoding RNA (lncRNA) in drug-resistant gastric cancer formation. First, we found that Notch 1 was highly expressed in the cisplatin-resistant gastric cancer cell lines SGC7901/DDP and BGC823/DDP cells. Then, we constructed a Notch 1 overexpression vector plasmid; after successful transfection, the SGC7901 and BGC823 cells highly expressed Notch 1. Moreover, the expression of multidrug resistance-associated protein 1 (MRP1), P-glycoprotein, increased significantly and the apoptosis of SGC7901 and BGC823 cells obviously reduced. We further screened out the lncRNA AK022798 involved in this process. Furthermore, we used siRNA to interfere with lncRNA AK022798 expression, and found that the expression of MRP1 and P-glycoprotein decreased significantly in SGC7901/DDP and BGC823/DDP cells, and their apoptosis as well as the expressions of caspase 3 and caspase 8 obviously increased. These results suggest that Notch 1 can promote the lncRNA AK022798 expression and result in the formation of SGC7901/DDP and BGC823/DDP cells. It may provide a new, useful method for gastric cancer chemotherapy.
Our findings identified VAMP8 as a novel oncogene by promoting cell proliferation and therapeutic resistance in glioma. Targeting VAMP8 may serve as a potential therapeutic regimen for the treatment of glioma.
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