No abstract

Objective:The aim of this study was to evaluate the mechanisms involved with miRNA-708 and its targeting of bone morphogenetic protein and activin membrane-bound inhibitor in cell proliferation, migration, and apoptosis in mice with melanoma via the Wnt and transforming growth factor β signaling pathways.Methods:Sixty mice were recruited of which 40 were subsequently assigned into the experimental group (22 mice were successfully established as melanoma model and 18 mice used in tumor xenograft), and the normal control group consisted of 20 mice. B16 cells were assigned to the normal, blank, and negative control, miR-708 mimics, miR-708 inhibitors, si-BAMBI, and miR-708 inhibitors + si-bone morphogenetic protein and activin membrane-bound inhibitor groups. Western blotting and reverse transcription quantitative polymerase chain reaction were employed to detect the expression levels within the tissues and cell lines. TCF luciferase reporter (TOP-FLASH) or a control vector (FOP-FLASH) was applied to detect the activity of the Wnt signaling pathway. MTT3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay, flow cytometry, scratch test, and Transwell assay were conducted, respectively, for cell proliferation, apoptosis, migration, and invasion, while tumor xenograft procedures were performed on the nude mice recruited for the study.Results:Compared to the normal control group, the model group displayed increased expressions of bone morphogenetic protein and activin membrane-bound inhibitor, Wnt10B, P53, and Bcl-2; TOPflash activity; β-catenin expression; cell proliferation; migration; and invasion capabilities while decreased expressions of miR-708, vascular endothelial growth factor, Fas, Bax, Caspase-3, and cleaved Caspase-3 and apoptosis rate. Compared to the blank and negative control groups, the miR-708 mimics and small-interfering RNA-bone morphogenetic protein and activin membrane-bound inhibitor groups exhibited decreases expressions of bone morphogenetic protein and activin membrane-bound inhibitor, Wnt10B, P53, and Bcl-2 and decreased proliferation, migration, and invasion capabilities, while increases in the apoptosis rate, expressions of vascular endothelial growth factor, Fas, Bax, Caspase-3, and cleaved Caspase-3; however, downregulated levels of TOPflash activity and β-catenin expression were recorded. The miR-708 inhibitors group displayed an opposite trend.Conclusion:Downregulation of miR-708-targeted bone morphogenetic protein and activin membrane-bound inhibitor inhibits the proliferation and migration of melanoma cells through the activation of the transforming growth factor β pathway and the suppression of Wnt pathway.

The key findings of this study provided evidence suggesting that miR-152 functions by means of binding to CTSL to induce GIST cell apoptosis and inhibit proliferation, migration, and invasion. The anti-tumor role of miR-152 makes it an attractive therapeutic target for GIST.

Background Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck region with poorly understood progression and prognosis. The present study aims at exploring whether the expression of β-catenin, TCF-4, and survivin affects clinicopathological features and prognostic significance in NPC. Methods We enrolled 164 patients with NPC and 70 patients with chronic nasopharyngitis (CNP) in this study. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) were conducted to evaluate the expression of β-catenin, TCF-4, and survivin. Spearman’s rank correlation analysis and Pearson correlation analysis were used to measure the correlation of β-catenin, TCF-4, and survivin. Risk factors for prognosis and survival conditions of NPC patients were analyzed by Cox proportional hazards model and Kaplan–Meier curves. Results The results obtained revealed that mRNA and protein expression of β-catenin, TCF-4, and survivin was higher in NPC tissues than in CNP tissues. Positive correlations amongst β-catenin, TCF-4, and survivin were identified by Spearman’s rank correlation analysis and Pearson correlation analysis. There was a significant correlation in expression of β-catenin, TCF-4, and survivin with EBV DNA, EBV-VCA-IgA, EBV-EA-IgA, T stage, N stage, and clinicopathological stages. Lower overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), and disease-free survival (DFS) rates were detected in NPC patients with positive expression of β-catenin, TCF-4, and survivin, in contrast to those with negative expression. Cox proportional hazards model demonstrated that β-catenin, TCF-4, and survivin protein positive expression were independent risk factors for OS and DFS of NPC prognosis; there was an evident correlation between clinicopathological stages, TCF-4, and EBV-EA-IgA and OS, DMFS, LRFS, and DFS of NPC. Conclusions The aforementioned results indicate that β-catenin, TCF-4, and survivin proteins are highly expressed in NPC, which can be used as factors to predict the malignancy of NPC. In addition, positive expression of β-catenin, TCF-4, and survivin are potential risk factors that lead to an unfavorable prognosis of OS and DFS in NPC patients.

Background Fairness has received much attention in our society. At present, the findings regarding fair decision-making in high-functioning autism spectrum disorder (HF-ASD) are inconsistent. Previous studies have shown that the fair decision-making of typically developing children is influenced by theory of mind (ToM) and executive functioning (EF). As those with HF-ASD have defects in both domains, this study aims to explore the differences in fair decision-making between children and adolescents with HF-ASD and those with typical development (TD). Methods We used a simple ultimatum game (UG) to explore 31 children and adolescents with HF-ASD and 38 children and adolescents with TD. T tests and chi-square tests were used to compare group differences, and Pearson correlation analysis and stepwise regression analysis were used to analyse the mechanisms influencing the two groups’ unfair acceptance rates. Results The results show that children with HF-ASD are more likely to accept unfair offers, but for adolescents, the difference is not significant. Regression analysis showed that the interaction between the behavior regulation index (BRI) and age could negatively predict the unfair acceptance rate of children and adolescents with HF-ASD. Working memory and ToM can negatively predict the unfair acceptance rate of those with TD. Conclusion This study concluded that the development of fair decision-making by children and adolescents with HF-ASD falls far behind that of those with TD. Intuition processes play a dominant role in the fair decision-making processes of children and adolescents with HF-ASD, and we believe that comorbidity, age, experience and emotional management are important factors influencing the fair decision-making of individuals with HF-ASD.