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Aberrant expression of microRNAs hae been shown to be closely associated with glioblastoma cell proliferation, apoptosis and drug resistance. However, mechanisms underlying the role of mcroRNAs in glioblastoma cell growth and apoptosis are not fully understood. In this study, we report that miR-503 is overexpressed in glioblastoma tissue compared with normal human brain tissue. Mechanistically, miR-503 can be induced by TGF-â1 at the transcriptional level by binding the smad2/3 binding elements in the promoter. Ectopic overexpression of miR-503 promotes cell growth and inhibits apoptosis by targeting PDCD4. In contrast, inhibition of miR-503 reduces cell growth. Furthermore, miR-503 inhibitor augments the growth inhibitory effect of temozolomide in glioblastoma cells. These results establish miR-503 as a promising molecular target for glioblastoma therapy.

Cerebral ischemic stroke may cause a number of adverse neurological complications or behavioral disorders. Moreover, cerebral ischemic stroke is a prevalent disease with limited treatment strategies and may increase chances of developing neurodegenerative diseases, e.g., Alzheimer's disease, in the future. Therefore, alternative strategies are highly needed for improving the therapy for ischemic stroke. Human bone marrow stroma stem cells, also known as mesenchymal stem cells (hMSC), have a demonstrative role in treating transient cerebral ischemia, yet whether immortalized hMSC may have a better effect than hMSC is unknown. Here, we addressed this question. A rat cerebral ischemia reperfusion (IR) model was used to compare the effects of hMSC and an immortalized hMSC by human telomerase reverse transcriptase (hMSC-TERT). We found that both hMSC and hMSC-TERT similarly attenuated the elevation of serum neuron specific enolase levels after IR. Transplantation with hMSC alleviated cerebral infarction, alleviated brain edema, improved neural function, and reduced brain cell apoptosis, in a significantly better degree than transplantation with hMSC. Thus, these data suggest that immortalized hMSC may have an advantage over hMSC in treatment of transient cerebral ischemia. [ABSTRACT FROM AUTHOR]

Purpose: Aplysin, a natural brominate compound from marine organisms, has been demonstrated to exhibit anti-tumor activity, mainly by inducing apoptosis and cell cycle arrest. However, its effect on glioma is still unknown. In this study, we evaluated the effects of aplysin on the malignant properties of glioma cells and its enhancing effect on temozolomide (TMZ) action against drug-resistant glioma cell lines. Methods: We employed several human glioma cell lines and primary glioma cells to address this issue with multidisciplinary approaches. Results: The combined application of aplysin and TMZ significantly sensitizes glioma cells to TMZ action, compared with TMZ alone. miRNA profile analysis revealed that the abundance of miR-181, an important glioma tumor suppressors believed to enhance TMZ effect, was greatly elevated in aplysin-treated glioma cell lines. The aplysin-induced TMZ sensitivity is dependent on MEK1 in glioma cells. Overexpression of MEK1 was able to abolish the effect of aplysin on glioma cells. Conclusions: We found that aplysin can enhance the effect of TMZ on glioma cells by increasing miR-181 expression. [ABSTRACT FROM AUTHOR]