The Circular RNA circSKA3 Facilitates the Malignant Biological Behaviors of Medulloblastoma via miR-520 h/CDK6 Pathway.

Circular RNAs (circRNAs) are reported to participate in the development of diverse human malignancies. This work investigated the mechanism of circSKA3 in modulating medulloblastoma progression. A total of 15 cases of medulloblastoma were collected in this work. Daoy cells were used to construct cell models. The expression level of circSKA3, microRNA-520 h (miR-520 h), and cyclin-dependent kinase 6 (CDK6) mRNA in tissues or cells was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was employed to detect CDK6 protein expression. CCK-8 experiment, Transwell assay, and flow cytometry were applied to detect the regulatory effects of circSKA3 on cell proliferation, migration, invasion, and cell cycle. Dual-luciferase reporter gene experiment was executed to determine the relationship between circSKA3 and miR-520 h, and between miR-520 h and CDK6. circSKA3 was remarkably up-modulated in medulloblastoma tissues. CircSKA3 depletion markedly suppressed Daoy cell viability, migration, invasion, and cell cycle progression. CircSKA3 overexpression induced the opposite effects. circSKA3 could decoyed miR-520 h, which targeted the 3' UTR of CDK6. circSKA3 expression in medulloblastoma tissues was negatively correlated with miR-520 h expression and positively correlated with CDK6 expression. "Rescue" experiments revealed that miR-520 h down-modulation or CDK6 overexpression remarkably counteracted the inhibitory effect of circSKA3 knockdown on Daoy cells. circSKA3 facilitates medulloblastoma progression through miR-520 h/CDK6.

A Promising Glycolysis- and Immune-Related Prognostic Signature for Glioblastoma.

BACKGROUND: Glioblastoma multiforme (GBM) is a malignant brain tumor with a poor prognosis. Aerobic glycolysis and an immunosuppressive microenvironment are potentially correlated with progression of GBM. However, the prognostic value of glycolysis-immune-related genes has not been studied in GBM. METHODS: Using GBM-related data downloaded from Chinese Glioma Genome Atlas database, the overlapped differentially expressed genes were identified between the GBM patients with a different glycolysis status and immune score, which had also undergone functional enrichment. Univariate Cox regression analysis and LASSO (least absolute shrinkage and selection operator) Cox regression analysis were used for risk score construction. Multivariate Cox regression analysis and survival analysis determined the independent prognostic factors. RESULTS: We found 277 overlapped differentially expressed genes between high glycolysis and low glycolysis, a high immune score and low immune score, and a combination of low glycolysis status and a low immune score and high glycolysis status and a high immune score. These were significantly enriched in 301 gene otology terms and 25 Kyoto Encyclopedia of Genes and Genomes pathways. Of these, 8 genes were found to be optimal for building a risk score. The risk score was an independent prognostic factor for GBM patients, and patients with a high score had a worse prognosis. Moreover, between the high- and low-risk GBM patients, 17 types of immune cells were differentially infiltrated, and 5 immune checkpoints were differentially expressed. CONCLUSIONS: The glycolysis-immune-related risk score using CACNG2, CSMD3, GABRA3, KCNIP2, KSR2, PTPRT, TNFRSF12A, and TNR was able to predict the prognosis of GBM patients relatively reliably.

Bilateral remote cerebellar hemorrhage following surgical clipping a ruptured supratentorial aneurysm.

Remote cerebellar hemorrhage (RCH) is a rare and severe complication after supratentorial surgery, with various risk factors and mechanisms remaining uncertain. Herein, we report a 64-year-old female patient suffered bilateral RCH following surgical clipping a ruptured aneurysm of internal carotid artery bifurcation. RCH is considered as venous in origin, and is likely the result of intra-operative or post-operative loss of CSF. Thus, appropriate control and close monitor the intra-operative and post-operative loss of CSF is of great importance for preventing the occurrence of RCH.

Human peripheral blood-derived mesenchymal stem cells with NTRK1 over-expression enhance repairing capability in a rat model of Parkinson's disease.

The potency of mesenchymal stem cells (MSCs) for tissue repair and regeneration is mainly based on their ability to secret beneficial molecules. Administration of MSCs has been proposed as an innovative approach and is proved by a number of clinical trials to a certain degree for the therapy of many diseases including Parkinson's disease (PD). However, the efficacy of MSCs alone is not significant. We investigated the effect of neurotrophic tyrosine receptor kinase 1 (NTRK1) overexpressed peripheral blood MSCs (PB-MSCs) on PD rat model. NTRK1 was overexpressed in PB-MSCs, which were then injected into PD rat model, Dopaminergic (DA) neuron regeneration and rotational performance was assessed. We found that DA neuron repair was increased in lesion site, rotational performance was also improved in MSC transplanted PD rat, with most potent effect in NTRK1 overexpressed PB-MSC transplanted PD rat. Our results indicate that overexpression of NTRK1 in MSCs could be an optimized therapeutic way via MSCs for PD treatment.

Dual Functional MicroRNA-186-5p Targets both FGF2 and RelA to Suppress Tumorigenesis of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is one of the most malignant cancers. MicroRNAs (miRs) were reported to play important roles in GBM recently. However, the role of a novel miR-186-5p in GBM tumorigenesis is still elusive. Using bioinformatics, miR-186-5p was identified as potential regulators of both fibroblast growth factor (FGF)-2 and NF-κB subunit RelA. Luciferase reporter assay was used to confirm the direct recognition FGF2 and RelA mRNAs by miR-186-5p. Invasion and migration assays were employed to study the effect of miR-186-5p on GBM cell growth in vitro. Xenograft tumor animal model was established to elucidate the in vivo function of miR-186-5p. MiR-186-5p directly targeted mRNAs of both FGF2 and RelA, and repressed their expressions. Invasive and migratory abilities of GBM cells and growth of xenograft tumors were significantly inhibited by miR-186-5p, which can be restored by re-introduction of FGF2 and RelA expressions. MiR-186-5p is a novel tumor suppressor miR that functions to inhibit tumorigenesis of GBM both in vitro and in vivo, by targeting both FGF2 and RelA. MiR-186-5p/FGF2/RelA pathway may be potentially used as molecular targets of in the clinical treatment of GBM.

miR-15b Inhibits the Progression of Glioblastoma Cells Through Targeting Insulin-like Growth Factor Receptor 1.

The microRNAs (miRNAs) have been suggested as a tumor suppressor in recent years. miR-15b was reported to exert an anti-oncogenic role in the proliferation, migration, and invasion of diverse tumor cells. However, the mechanisms underlying miR-15b-mediated biology of glioblastoma are still unclear. In the present study, the expression of miR-15b was down-regulated in glioblastoma tumor tissues and U87 and U251 cells, but insulin-like growth factor receptor 1 (IGF1R) expression became up-regulated in these tumor tissues and cells (all p < 0.001). Furthermore, IGF1R expression was inversely associated with miR-15b expression. Notably, patients with lower miR-15b expression have a much shorter survival period compared with high expression (log-rank test p = 0.045). In vitro data demonstrated that miR-15b mimics inhibited the proliferation, cell cycle arrest, and invasion of U87 and U251 cells. Besides, we validated IGF1R as a direct target of miR-15b using dual luciferase assays, and IGF1R plasmids partially abrogated miR-15b mimics inhibited cell proliferation. In vivo, miR-15b mimics indeed repressed cell proliferation in mouse xenograft model. In conclusion, our study demonstrated that miR-15b inhibits the progression of glioblastoma cells through targeting IGF1R, and miR-15b can be recommended as a tumor suppressor in the progression of glioblastoma.

MicroRNA-520b affects the proliferation of human glioblastoma cells by directly targeting cyclin D1.

Glioblastoma (GBM) represents one of most common tumors in humans. However, the biological processes and molecular mechanisms of GBM are still unclear. It is known that microRNA-520b (miR-520b) participates in the development of various tumor progressions. The present study was to evaluate the level of miR-520b in GBM tissues and cells. We further investigated the molecular mechanisms of miR-520b in U87 and U251 cell lines. Here, our data showed that the expression levels of miR-520b were significantly reduced in clinical GBM tissues and cell lines. Accordingly, the expression levels of cyclin D1 were significantly increased in clinical GBM tissues and cell lines. Ectopic expression of miR-520b in U87 and U251 cells resulted in decreased cell proliferation and enhanced cell apoptosis. Further study characterized the 3' untranslated region (3'-UTR) of cyclin D1 gene as a direct target of miR-520b in U87 and U251 cells as determined by luciferase reporter assays. In addition, ectopic expression of miR-520b led to the down-regulation of phosphorylated retinoblastoma (p-Rb, a downstream effector of cyclin D1), while the overexpression of cyclin D1 reversed the miR-520b-induced inhibition of p-Rb expression. In conclusion, this study highlights the importance of miR-520b in regulating the proliferation and apoptosis of GBM by directly targeting cyclin D1, and miR-520b may represent a potential therapeutic strategy for GBM.