Gliomas are the most common type of primary brain tumor in the central nervous system of adults. Maternally Expressed Gene 3 (MEG3) is an imprinted gene located at 14q32 that encodes a non-coding RNA (ncRNA) associated with tumorigenesis. However, little is known about whether and how MEG3 regulates glioma development. In the present study we assayed the expression of MEG3 in glioma tissue samples by real-time polymerase chain reaction assay, and defined the biological functions and target genes by CCK-8 assay, flow cytometry, and RNA immunoprecipitation. We first demonstrated that MEG3 expression was markedly decreased in glioma tissues compared with adjacent normal tissues. Moreover, ectopic expression of MEG3 inhibited cell proliferation and promoted cell apoptosis in U251 and U87 MG human glioma cell lines. We further verified that MEG3 was associated with p53 and that this association was required for p53 activation. These data suggest an important role of MEG3 in the molecular etiology of glioma and implicate the potential application of MEG3 in glioma therapy.

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Introduction: MCM3AP-AS1 has been characterized as an oncogenic lncRNA in several types of cancer, while its role in nasopharyngeal carcinoma (NPC) is unknown. This study aimed to investigate the role of MCM3AP-AS1 in NPC. Patients and Methods: Paired NPC tissues and non-tumor tissues were collected from 55 NPC patients. Expression of MCM3AP-AS1 and miR-34a in paired tissues was analyzed by RT-qPCR. Interactions between MCM3AP-AS1 and miR-34a were analyzed by overexpression experiments. The roles of MCM3AP-AS1 and miR-34a in regulating NPC cell proliferation and apoptosis were explored by cell proliferation assay and cell apoptosis assay, respectively. Results: Our bioinformatics analysis showed that MCM3AP-AS1 may be targeted by miR-34a, which is a well-studied tumor suppressor miRNA. In this study, we showed that miR-34a was downregulated and MCM3AP-AS1 was upregulated in NPC. An inverse correlation between the expression of MCM3AP-AS1 and miR-34a was found across NPC tissue samples. High expression level of MCM3AP-AS1 and low levels of miR-34a in NPC tissues predicted the poor survival. In NPC cells, overexpression of MCM3AP-AS1 did not affect the expression of miR34a, while overexpression of miR-34a led to downregulated MCM3AP-AS1. Cell proliferation and apoptosis assay showed that overexpression of miR-34a reduced the enhancing effects of overexpressing MCM3AP-AS1 on cell proliferation and the inhibitory effects on cell apoptosis. Conclusion: MiR-34a inhibits cell proliferation and induces apoptosis in human NPC by targeting MCM3AP-AS1.

Matrix metalloproteinase 3 (MMP-3) is implicated in the pathogenesis and progression of glioma. However, whether MMP-3 participates in the regulation of metastasis and its mechanisms in glioma is mostly unknown. In the present study, glioma cells were stably transfected with Bmi-1 small interfering RNA (siRNA) to knockdown off Bmi-1 or were transiently transfected with Bmi-1 complementary DNA (cDNA) to upregulate the Bmi-1 level and to evaluate their effects on invasion and expression analysis for molecules involved in invasion. Knockdown of Bmi-1 dramatically reduced a nuclear factor kappa B (NF-κB) and MMP-3 expression and activity in T98G cells. When the T98G cells were upregulated in the Bmi-1 levels, the T98G cells were treated with 10 μM BAY 11-7028 to inhibit the NF-κB activity. The invasion induced by upregulation of Bmi-1 was severely abolished by BAY 11-7028 in Bmi-1 overexpression cells. The T98G cell metastatic potential was increased by overexpression of Bmi-1; completely at the same time, the NF-κB activity and MMP-3 expression was also increased. Taken together, these findings suggest that Bmi-1 promotes glioma cell migration and invasion via NF-κB-mediated upregulation of MMP-3.

BackgroundAcid–base imbalance in various metabolic disturbances leads to human brain dysfunction. Compared with acidosis, the patients suffered from alkalosis demonstrate more severe neurological signs that are difficultly corrected. We hypothesize a causative process that the nerve cells in the brain are more vulnerable to alkalosis than acidosis.MethodsThe vulnerability of GABAergic neurons to alkalosis versus acidosis was compared by analyzing their functional changes in response to the extracellular high pH and low pH. The neuronal and synaptic functions were recorded by whole-cell recordings in the cortical slices.ResultsThe elevation or attenuation of extracellular pH impaired these GABAergic neurons in terms of their capability to produce spikes, their responsiveness to excitatory synaptic inputs and their outputs via inhibitory synapses. Importantly, the dysfunction of these active properties appeared severer in alkalosis than acidosis.ConclusionsThe severer impairment of cortical GABAergic neurons in alkalosis patients leads to more critical neural excitotoxicity, so that alkalosis-induced brain dysfunction is difficultly corrected, compared to acidosis. The vulnerability of cortical GABAergic neurons to high pH is likely a basis of severe clinical outcomes in alkalosis versus acidosis.