[Retracted] miR­218 inhibits the migration and invasion of glioma U87 cells through the Slit2­Robo1 pathway.

[This retracts the article DOI: 10.3892/ol.2015.2904.].

Increased serum concentrations of signal peptide-Cub-Egf domain-containing protein-1 in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Signal peptide-Cub-Epidermal growth factor domain-containing protein 1 (SCUBE1), a marker for coagulation, is correlated with prognosis of some critical illnesses. The current study was designed to investigate the potential prognostic value of serum SCUBE1 concentrations in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Serum SCUBE1 concentrations of 125 patients and 125 controls were determined. Multivariate analyses were performed to identify independent risk factors for 6-month mortality, overall survival and unfavorable outcome (Glasgow Outcome Scale score of 1-3). RESULTS: Serum SCUBE1 concentrations were significantly higher in patients than in controls (17.7±7. vs. 1.2±0.4ng/ml, P<0.001) and were associated highly with World Federation of Neurological Surgeons (WFNS) scores (t=5.109, P<0.001) and modified Fisher scores (t=4.329, P<0.001). SCUBE1 emerged as an independent predictor for 6-month clinical outcomes. It had similar area under receiver operating characteristic curve (AUC) to WFNS scores and modified Fisher scores. Moreover, it could markedly improve the AUC of WFNS scores and modified Fisher scores to predict 6-month unfavorable outcome. CONCLUSION: Enhanced SCUBE1 concentrations are correlated with increasing severity and poor outcomes of aSAH patients, indicating SCUBE1 might have the potential to identify aSAH patients at risk of poor prognosis.

MiR-218 inhibits the tumorgenesis and proliferation of glioma cells by targeting Robo1.

BACKGROUND: Malignant glioma is the most common primary brain tumors directly correlated with the high mortality and poor prognosis in clinical practice. MicroRNAs (miRNAs or miRs) influence numerous cancer-relevant processes including cell proliferation, differentiation and metabolism. However, the role of microRNA in malignant glioma is largely unknown. This study aimed to study the role of miR-218, a tumor-suppressive microRNA, in glioma development both in vivo and in vitro. METHODS: The expression level of miR-218, Slit2 and Robo1 was examined by either quantitative (polymerase chain reaction) or western-blotting from both human glioma tissue and glioma cell lines. U87 cells were transfected with miR-218 and then the expression levels of Slit2 and Robo1 were quantified. Cell proliferation was measured both by the in vitro proliferation assay and in vivo graft studies. The luciferase reporter assay was employed to validate the downstream target of miR-218. RESULTS: The expression of miR-218 was lower in glioma cell lines and glioma tissues from the patients with decreased Slit2 and increased Robo1 protein levels. The over-expression of miR-218 inhibited the tumorgenesis and proliferation of glioma cells remarkably. Furthermore, the over-expressing miR-218 in glioma cells results in the downregulation of Robo1 and upregulation of Slit2. Using luciferase reporter assays, we found that Robo1 was a direct downstream target of miR-218. CONCLUSION: Over-expression of miR-218 in glioma cells may inhibit the proliferation and tumorigenicity through targeting Robo1, suggesting that miR-218 could be a potential target for developing therapies in treating glioma.

miR-218 inhibits the migration and invasion of glioma U87 cells through the Slit2-Robo1 pathway.

Malignant gliomas are the most common primary brain tumors in adults and are associated with the highest mortality rate. Glioma invasion is one of the most notable causes of the poor prognosis of this cancer. Preventing the invasive behavior of malignant glioma cells by altering effector molecules can significantly improve the prognosis of a patient. microRNAs (miRNAs) are small noncoding RNAs, ~22 nucleotides in length, that are able to function as oncogenes or tumor suppressors in human cancer. In the present study, the expression level of miRNA 218 (miR-218) was found to be markedly downregulated in glioma cell lines and human primary glioma tissues. miR-218 upregulation was found to dramatically reduce the migratory speed and invasive ability of glioma cells. Furthermore, it was demonstrated that ectopic expression of miR-218 in glioma cells resulted in the downregulation of roundabout, axon guidance receptor, homolog 1 (Robo1), upregulation of Slit homolog 2 (Slit2) and the expression of associated proteins following Robo1 knockdown by small interfering RNA. In addition, it was demonstrated that miR-218 inactivated the Slit2-Robo1 pathway through downregulating Robo1 expression by directly targeting the 3'-untranslated region (3'-UTR) of Robo1. The present results indicate that miR-218 plays important roles in preventing the invasiveness of glioma cells, and reveals a novel mechanism of miRNA-mediated direct suppression of the Slit2-Robo1 pathway in glioma.