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Glioblastoma multiforme (GBM) is a highly malignant cancer in the brain with a median survival time of approximately one year. However, the mechanisms underlying GBM development and occurrence are poorly understood. Recently, miRNAs were reported to play important roles in GBM. We performed microRNA profiling by comparing the human GBM cell line T98G and control cell line HCN1A. MicroRNA assays, PCR and Western blot analysis were performed to detect the expressions of microRNAs, mRNAs and proteins of target genes, respectively. Cell migration and invasion assays were conducted. A murine in situ xenograft tumor model was used to evaluate tumor growth in vivo. Glioblastoma tissues were examined to investigate the clinical relevance of our findings. MiR-302d and miR-16 levels were found to be decreased in T98G cells. MiR-302d and miR-16 inhibited the expressions of p65 and FGF2, respectively, by binding to the 3'-UTR of their mRNAs. Over-expression of miR-302d and miR-16 inhibited T98G cell migration and invasion in vitro, and tumorigenesis in the xenograft tumor mouse model in vivo, by suppressing p65 and FGF2. Negative correlations between miR-302d and p65 and between miR-16 and FGF2 were observed in patient glioblastoma tissues. MiR-302d and miR-16 inhibit tumorigenesis by down-regulating p65 and FGF2, which potentially contributes to the treatment of glioblastoma with clinical relevance.

Resveratrol is a naturally occurring phytoalexin found in red grapes, and believed to have neuroprotective, anti-oxidant, and anti-inflammatory effects. But little is known about its effect on the neural impairments induced by microglial over-activation, which leads to neuroinflammation and multiple pathophysiological damages. In this study, we aimed to investigate the protective effects of resveratrol on the impairments of neural development by microglial over-activation insult. The results indicated that resveratrol inhibited the lipopolysaccharide (LPS)-dependent release of cytokines from activated microglia and LPS-dependent changes in NF-κB signaling pathway. Conditioned medium (CM) from activated microglia treated by resveratrol directly protected primary cultured hippocampal neurons against LPS-CM-induced neuronal death, and restored the inhibitory effects of LPS-CM on dendrite sprouting and outgrowth. Finally, neurons cultured in CM from LPS-stimulated microglia treated by resveratrol exhibited increased spine density compared to those without resveratrol treatment. Our findings support that resveratrol inhibits microglial over-activation and alleviates neuronal injuries induced by microglial activation. Our study suggests the use of resveratrol as an alternative intervention approach that could prevent further neuronal insults. [ABSTRACT FROM AUTHOR]