The miR-141/neuropilin-1 axis is associated with the clinicopathology and contributes to the growth and metastasis of pancreatic cancer.

BACKGROUND: Neuropilin-1 (NRP-1) is a non-tyrosine kinase receptor interacting with multiple signaling pathways that underpin the biological behavior and fate of cancer cells. However, in pancreatic cancer, the mechanisms underlying the function of NRP-1 in cell proliferation and metastasis and the involvement of regulatory upstream miRNAs remain unclear. METHODS: Potential miRNAs were mined by using multiple bioinformatics prediction tools and validated by luciferase assays. The expression of NRP-1 and miRNA-141 (miR-141) in pancreatic tissues and cells was examined by immunohistochemistry, immunoblotting and/or real-time RT-PCR. Stable transfected cells depleted of NRP-1 were generated, and regulatory effects of miR-141 were investigated by transfecting cells with miR-141 mimics and anti-miR-141. Assays of cell viability, proliferation, cell cycle distribution, transwell migration and cell scratch were employed. Xenograft tumor models were established to assess the effects of NRP-1 depletion on tumorigenesis and liver metastasis, and therapeutic effects of miR-141 on tumor growth. The role of miR-141/NRP-1 axis in regulating epithelial-mesenchymal transition (EMT) by co-interacting the TGF-ß pathway was examined. RESULTS: In this study, of 12 candidate miRNAs identified, miR-141 showed the strongest ability to regulate NRP-1. In pancreatic cancer tissues and cells, the expression level of NRP-1 was negatively correlated with that of miR-141. NRP-1 was highly expressed in pancreatic cancer tissues compared with normal pancreatic tissues, and its expression levels were positively correlated with tumor grade, lymph metastasis and AJCC staging. NRP-1 depletion inhibited cell proliferation by inducing cell cycle arrest at the G0/G1 phase through upregulating p27 and downregulating cyclin E and cyclin-dependent kinase 2, and reduced cell migration by inhibiting EMT through upregulating E-cadherin and downregulating Snail and N-cadherin. Through downregulating NRP-1, miR-141 mimics showed a similar effect as NRP-1 depletion on cell proliferation and migration. NRP-1 depletion suppressed tumor growth and liver metastasis and miR-141 mimics inhibited the growth of established tumors in mice. NRP-1 depletion and/or miR-141 mimics inhibited the activation of the TGF-ß pathway stimulated by TGF-ß ligand. CONCLUSIONS: The present results indicate that NRP-1 is negatively regulated by miR-141 and the miR-141/NRP-1 axis may serve as potentially valuable biomarkers and therapeutic targets for pancreatic cancer.

Analysis of risk factors of gastrointestinal stromal tumors in different age groups based on SEER database.

Objective: To investigate the risk factors affecting the survival of patients with gastrointestinal stromal tumors (GISTs) in different age groups. Methods: Information on 6089 GIST patients was screened from the Surveillance, Epidemiology, and End Results (SEER) database. Risk factor analysis was performed using a chi-square test (univariate analysis). Survival analysis was performed using the Kaplan-Meier method (log-rank test) and the COX proportional hazard model. p Value < .05 was considered statistically significant. Results: Analyzed statistically to reveal that in addition to tumor size, mitotic index, and primary location, age, gender, race, and surgical treatment also were independent risk factors for GISTs. Gender, race, and location of disease influenced the survival rate of patients, which was higher in the young group (≤60 years old) than the elderly group (>60 years). Risk factors such as primary location, tumor diameter, and mitotic index varied significantly between the different age groups. Conclusions: Age, gender, race, and surgical treatment are independent risk factors that influence the prognosis in patients with GISTs. Some risk factors affecting prognosis are age dependent.

The correlation between magnetic resonance imaging features of the brainstem and cerebellum and clinical features of spinocerebellar ataxia 3/Machado-Joseph disease.

BACKGROUND: Brainstem and cerebellar atrophy are the most important features in magnetic resonance imaging (MRI) in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD). However, the correlation between brainstem and cerebellar atrophy and the clinical features has not been well studied. AIM: To study the correlation between MRI features of the brainstem and cerebellum and predominant clinical features in SCA3/MJD. DESIGN AND SETTING: University teaching hospital. PATIENTS AND METHODS: By using the linear measurement method, we assessed 32 patients with SCA3/MJD to study the correlations between the morphometric data of the brainstem and cerebellum and clinical features: Duration of the disease, age of onset, total international cooperative ataxia rating scale (ICARS) score; total scale for the assessment and rating of ataxia (SARA) score; ICARS subscores, and SARA subscores. STATISTICAL ANALYSIS: Pearson correlation test. RESULTS: There was a significant inverse correlation between anteroposterior diameter of the midbrain and pons and total ICARS scores, total SARA scores, ICARS and SARA subscores (r = -0.381 approximately -0.57, P < 0.05 or 0.01) and disease duration (r = -0.42 approximately -0.51, P < 0.05 or 0.01). Additionally, superoinferior diameter of the cerebellum was inversely correlated with total SARA scores and ICARS and SARA subscores except for ataxia of posture and gait in both scales (r = - 0.37 approximately -0.44, P < 0.05). The superoinferior diameter of the fourth ventricle was inversely correlated with age of onset (r = -0.45, P < 0.05). CONCLUSION: The effect on the cerebellum and brainstem is related to predominant clinical features in SCA3/MJD patients.