Changes of arachnoid granulations after subarachnoid hemorrhage in cynomolgus monkeys.

This research explores ultrastructural changes of arachnoid granulations associated with hydrocephalus after subarachnoid hemorrhage in cynomolgus monkeys. It provides a theoretical basis for further study of the etiology and prevention of hydrocephalus. Female cynomolgus monkeys about one-year-old were selected. The position range of arachnoid granulations in superior sagittal sinus and transverse sinus was determined in a randomly selected control monkey. The morphology of normal arachnoid granulations in cynomolgus monkeys was observed under a transmission electron microscope. A primate model of subarachnoid hemorrhage was established by injecting autologous blood into cisterna magna. Vomiting, movement disorder, and reduced level of consciousness were gradually observed in monkeys. Computed tomography and magnetic resonance imaging scan results confirmed subarachnoid hemorrhage and hydrocephalus, and the morphology of arachnoid granulations in hydrocephalus was observed under a transmission electron microscope. Extensive fibrosis of arachnoid granulations was observed under a transmission electron microscope in cynomolgus monkeys with hydrocephalus after subarachnoid hemorrhage.

MiR-501-5p acts as an energetic regulator in head and neck squamous cell carcinoma cells growth and aggressiveness via reducing CLCA4.

Recent research have proved that miR-501-5p acted as a potent tumor biomarker in several cancers, excluding head and neck squamous cell carcinoma (HNSCC). The study intends to discover the potential function and mechanism of miR-501-5p in HNSCC. Data from TCGA database and qRT-PCR estimated the expression of miR-501-5p and Calcium activated Chloride Channel A4 (CLCA4). Cell proliferation, clone formation and transwell assays were performed to explore HNSCC cells biological behaviors. Luciferase assay was carried out to identify the interaction between miR-501-5p and CLCA4. miR-501-5p was profoundly up-regulated in HNSCC samples and promoted cells proliferation and metastasis. CLCA4, as a target of miR-501-5p, was connected with worse outcomes in HNSCC patients. Co-transfection assay proved that miR-501-5p/CLCA4 functioned as crucial regulators to affect HNSCC cells biological behaviors. Our study illustrated that miR-501-5p exhibited a tumor-promoting role on HNSCC by targeting CLCA4, providing a new insight for revealing the pathogenesis and treatment of HNSCC.

MiR-188-3p/GPR26 modulation functions as a potential regulator in manipulating glioma cell properties.

Background: Glioblastoma (GBM) is recognized as a malignant brain tumor with frequent mortality. Extensive evidence indicated that miR-188-3p exerts an important role in various tumors. However, the role of miR-188-3p in GBM has not been elucidated. The purpose of the present investigation was to explore the biological effect of miR-188-3p, as well as to determine its target gene in GBM.Methods: The miR-188-3p and G Protein-Coupled Receptor 26 (GPR26) expressional profiles were obtained from The Cancer Genome Atlas (TCGA) database. The proliferative ability, invasive and migratory capabilities of GBM cells were measured using Cell Counting Kit-8 and transwell assays. Bioinformatics tool and luciferase reporter gene analysis were utilized to assess the correlation between miR-188-3p and GPR26. Reverse transcription-quantitative polymerase chain reaction (RT-PCR) and western blotting were performed to detect the indicated gene expression.Results: MiR-188-3p expression was highly regulated in GBM tissue and cell lines, while GPR26 was significantly decreased in GBM. Depletion of miR-188-3p significantly retarded the cell proliferation, invasion and migration in the U-87 MG cell. Luciferase reporter gene assay showed that GPR26 was a target gene of miR-188-3p in GBM. The expression of GPR26 was negatively regulated by miR-188-3p. The inhibitory effect of miR-188-3p inhibitor on cell behaviors was further strengthened by the overexpression of GPR26 in GBM.Conclusion: These findings provided evidence for the cancer-promoting effect of miR-188-3p in GBM cells and demonstrated that GPR26 was directly targeted by miR-188-3p, which might contribute to the therapeutic therapy of GBM.

RBM5 inhibits tumorigenesis of gliomas through inhibition of Wnt/ß-catenin signaling and induction of apoptosis.

BACKGROUND: Gliomas are one of the most common malignant brain tumors and bring a big threat to human life as traditional therapy is unsatisfactory. RBM5 was a RNA-binding motif protein and was reported as a tumor suppressor. But the role of RBM5 in gliomas was unknown. METHODS: The mRNA level of RBM5 was determined in gliomas tissues and cell lines by real-time quantitative PCR (qRT-PCR) assay while the association of RBM5 expression with prognosis was analyzed by Kaplan-Meier method and compared by log-rank test. Lentivirus was used to overexpress RBM5 in gliomas cells. MTT and BrdU incorporation assay were used to determine cell proliferation and DNA synthesis when the ability of cell migration and invasion was analyzed by transwell assay with/without Matrigel. Cell apoptosis rate was determined with fluorescence-activated cell sorting (FACS) method. Then, expression of apoptosis molecules and critical members in Wnt/ß-catenin pathway were detected by western blot analysis. RESULTS: RBM5 was shown to be downregulated in gliomas tissues and gliomas cell lines. And decreased RBM5 expression was clinically correlated with tumor stage, patient age, and poor prognosis of gliomas patients. The proliferation and DNA synthesis was dramatically inhibited when RBM5 was overexpressed in SHG44 or U251 cells. Also, the ability of cell migration and invasion was disrupted. Then, the level of ß-catenin and Cyclin D1 significantly decreased when DKK1 and P-GSK-3ß increased reversely in SHG44 cells, which suggested that RBM5 inhibited canonical Wnt/ß-catenin signaling. Meanwhile, we demonstrated that caspase3-mediated apoptotic pathway was activated by RBM5 as Bax, TNF-α, and cleaved caspase3 were greatly upregulated while antiapoptotic molecule Bcl-2 was downregulated. Additionally, that apoptotic rate increased significantly from less than 1 to 32% in RBM5-overexpressed SHG44 cells further supported the pro-apoptosis role of RBM5 in gliomas cells. CONCLUSIONS: RBM5 plays a suppressor role in human gliomas by inhibiting Wnt/ß-catenin signaling and inducing cell apoptosis. This study improves our knowledge about the carcinogenesis and progression of human gliomas, which would greatly contribute to the therapy for gliomas patients.