Recently, microRNAs (miRNAs), a kind of small and non-coding RNA, can target the downstream molecules. Increasing evidence demonstrates that miRNAs meditate the onset and progression of a variety of tumors. In the present study, we carried out gene transfection, western blot, and reverse transcription PCR (RT-PCR) to explore the role of miR-22 in glioblastoma tissues and cell lines. Here, we verified that the expression of miR-22 was downregulated in glioblastoma tissues and cells rather than matched non-tumor tissues and normal human astrocyte (NHA) cells (p < 0.001). By contrast, SIRT1 messenger RNA (mRNA) and protein were upregulated in glioblastoma tissues and cells (p < 0.001). In vitro miR-22 mimics interfered with cell proliferation, migration, and invasion of U87 and U251 cells. Mechanically, the 3'-untranslated regions (3'-UTRs) of SIRT1 were a direct target of miR-22, leading to the decreased expression of SIRT1 protein in U87 and U251 cells. Meanwhile, miR-22 mimics also inhibited the expression of epidermal growth factor receptor (EGFR) and matrix metallopeptidase 9 (MMP9). In conclusion, miR-22 inhibited cell proliferation, migration, and invasion via targeting the 3'-UTR of SIRT1 in the progression of glioblastoma and miR-22-SIRT1 pathway can be recommended as a potential target for treatment of glioblastoma.

Moyamoya disease (MMD) is a cerebrovascular disease characterized by progressive stenosis of the intracranial internal carotid arteries and their proximal branches. However, the etiology of this rare disease remains unknown. Serum microRNA (miRNA) profiles have been screened to identify novel biomarkers of prognostic values. Here, we identified serum miRNAs that might play an important role in the pathogenesis of MMD. A genome-wide miRNA array analysis of two pooled serum samples from patients with MMD and controls revealed 94 differentially expressed serum miRNAs, including 50 upregulated and 44 downregulated miRNAs. In an independent MMD cohort, real-time PCR confirmed that miR-106b, miR-130a and miR-126 were significantly upregulated while miR-125a-3p was significantly downregulated in serum. GO analysis showed that the differentially expressed serum miRNAs were enriched in metabolic processes, transcription and signal transduction. Pathway analysis showed that the most enriched pathway was mTOR signaling pathway with 16 potential, functional targets. Finally, we found that 16 and 13 aberrant serum miRNAs coordinately inhibited RNF213 and BRCC3 protein expression at the posttranscriptional level, respectively, resulting in defective angiogenesis and MMD pathogenesis. To our knowledge, this is the first study to identify a serum miRNA signature in MMD. Modulation of the mechanism underlying the role of serum miRNAs in MMD is a potential therapeutic strategy and warrants further investigations.

BackgroundMiR-106a is frequently down-regulated in various types of human cancer. However the underlying mechanism of miR-106a involved in glioma remains elusive.MethodsThe association of miR-106a with glioma grade and patient survival was analyzed. The biological function and target of miR-106a were determined by bioinformatic analysis and cell experiments (Western blot, luciferase reporter, cell cycle, ntracellular ATP production and glucose uptake assay). Finally, rescue expression of its target SLC2A3 was used to test the role of SLC2A3 in miR-106a-mediated cell glycolysis and proliferation.ResultsHere we showed that miR-106a was a tumor suppressor miRNA was involved in GBM cell glucose uptake and proliferation. Decreased miR-106a in GBM tissues and conferred a poor survival of GBM patients. SLC2A3 was identified as a core target of miR-106a in GBM cells. Inhibition of SLC2A3 by miR-106a attenuated cell proliferation and inhibited glucose uptake. In addition, for each biological process we identified ontology-associated transcripts that significantly correlated with SLC2A3 expression. Finally, the expression of SLC2A3 largely abrogated miR-106a-mediated cell proliferation and glucose uptake in GBM cells.ConclusionsTaken together, miR-106a and SLC2A3 could be potential therapeutic approaches for GBM.

No abstract

MicroRNAs are known to be involved in carcinogenesis and tumor progression in glioma. Recently, microRNA-372 (miR-372) has been proved to play a substantial role in several human cancers, but its functions in glioma remain unclear. In this study, we confirmed that miR-372 was commonly upregulated in glioma cell lines and tissues. Downregulation of miR-372 markedly inhibited cell proliferation and invasion and induced G1/S arrest and apoptosis. Consistently, the xenograft mouse model also unveiled the suppressive effects of miR-372 knockdown on tumor growth. Further studies revealed that miR-372 modulated the expression of PHLPP2 by directly targeting its 3'-untranslated region (3'-UTR) and that miR-372 expression was inversely correlated with PHLPP2 expression in glioma samples. Silencing of PHLPP2 could rescue the inhibitory effect of miR-372 inhibitor. Moreover, miR-372 knockdown suppressed the phosphorylation levels of the major components of PI3K/Akt pathway including Akt, mTOR, and P70S6K. Taken together, our results suggest that miR-372 functions as an oncogenic miRNA through targeting PHLPP2 in glioma.

OBJECTIVE The authors compared the contemporary perioperative procedure-related complications between coiling with stent placement and coiling without stent placement for acutely ruptured aneurysms treated in a single center after improvement of interventional skills and strategy. METHODS In an institutional review board-approved protocol, 133 patients who underwent coiling with stent placement and 289 patients who underwent coiling without stent placement from January 2012 to December 2014 were consecutively reviewed retrospectively. Baseline characteristics, procedure-related complications and mortality rate, angiographic follow-up results, and clinical outcomes were compared between the two groups. Univariate analysis and logistic regression analysis were performed to determine the association of procedure-related complications of coiling with stent placement with potential risk factors. RESULTS The coiling/stent group and coiling/no-stent group were statistically comparable with respect to all baseline characteristics except for aneurysm location (p < 0.001) and parent artery configuration (p = 0.024). The immediate embolization results and clinical outcomes between the two groups showed no significant differences (p = 0.807 and p = 0.611, respectively). The angiographic follow-up results of the coiling in stent group showed a significant higher occlusion rate and lower recurrence rate compared with the coiling/no-stent group (82.5% vs 66.7%, 3.5% vs 14.5%, p = 0.007). Procedure-related intraoperative rupture and thrombosis, postoperative early rebleeding and thrombosis, and external ventricular drainage-related hemorrhagic event occurred in 3.0% (4 of 133), 2.3% (3 of 133), 1.5% (2 of 133), 0.7% (1 of 133), and 0.8% (1 of 133) of the coiling/stent group compared with 1.0% (3 of 289), 1.4% (4 of 289), 1.4% (4 of 289), and 0.7% (2 of 289) of the coiling/no-stent group, respectively (p = 0.288, p = 0.810, p = 1.000, p = 0.315, and p = 1.000, respectively). One patient presented with coil protrusion in the group of coiling without stent. The procedure-related mortality was 1.5% (2 of 133) in the coiling/stent group and 0.7% in the coiling/no-stent group (p = 0.796). Multivariable analysis showed no significant predictors for the total perioperative procedure-related complications, hemorrhagic complications, or ischemic complications. CONCLUSIONS The perioperative procedure-related complications and mortality rate did not differ significantly between the coiling/stent group and the coiling/no-stent group for patients with acutely ruptured aneurysms. Considering the better angiographic follow-up results, coiling with stent placement might be a feasible, safe, and promising option for treatment in the acute phase of selected wide-necked ruptured intracranial aneurysms.

BackgroundAnalyzing risk factors for hyperperfusion-induced intracranial hemorrhage (HICH) after carotid artery stenting (CAS) in patients with symptomatic severe carotid stenosis.MethodsThis study retrospectively analyzed clinical data of 210 patients, who had symptomatic severe carotid stenosis (70–99%) and received CAS treatment between June 2009 and June 2015, and evaluated the relationship of HICH with patients’ clinical baseline data, imaging features, and treatment strategies.ResultsSeven patients (3.3%) developed HICH after CAS. The incidence of HICH among patients with near total occlusion was significantly higher than among those without (10.1% vs 0%, P<0.001). Out of the seven, five had no development of either anterior or posterior circulations, and two had no development of anterior circulation and poor development of posterior circulation. Results showed that patients with poor compensation of Willis’ Circle were more likely to develop HICH compared with other patients (P<0.001). All patients received preoperative CT perfusion. TTP index was defined as the TTP ratio between the affected and contralateral side. The results showed that the TTP index was significantly different between the HICH group and non-HICH group (1.15±0.10 vs 1.30±0.15, P<0.001). An analysis of the ROC curve indicated that patients with TTP index >1.22 were more likely to develop HICH compared with other patients (sensitivity 100%, specificity 75.9%).ConclusionsPatients with severe unilateral carotid stenosis, the presence of near total occlusion, poor compensation of Willis’ Circle, and preoperative TTP index>1.22, have a higher risk of developing HICH after CAS.

No abstract