M alignant gliomas are the most common type of primary malignant brain tumor, and more than half of all gliomas are glioblastomas (Grade IV astrocytoma), one of the most aggressive and lethal types of brain tumor. Glioblastoma cells easily infiltrate into the normal cerebral cortex, ultimately resulting in the death of the patient. Well-defined risk factors for glioblastoma include radiation exposure and certain genetic syndromes. 21Several molecular and genomic datasets have recently been generated that have allowed identification of at least 4 subtypes of glioblastoma: classical, mesenchymal, proneural, and neural.14 Previous studies in glioblastoma geabbreviatioNs FBS = fetal bovine serum; HCC = hepatocellular carcinoma; HUVEC = human umbilical vein endothelial cell; lncRNA = long noncoding RNA; ncRNA = noncoding RNA; RT-qPCR = real-time quantitative reverse transcription polymerase chain reaction; SD = standard deviation. 3 Department of Respiratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing; and 4 Department of Oncology, The Second Affiliated Hospital of Suzhou University, Suzhou, China obJective Increased levels of H19 long noncoding RNA (lncRNA) have been observed in many cancers, suggesting that overexpression of H19 may be important in the development of carcinogenesis. However, the role of H19 in human glioblastoma is still unclear. The object of this study was to examine the level of H19 in glioblastoma samples and investigate the role of H19 in glioblastoma carcinogenesis. methods Glioblastoma and nontumor brain tissue specimens were obtained from tissue obtained during tumor resection in 30 patients with glioblastoma. The level of H19 lncRNA was detected by real-time quantitative reverse transcription polymerase chain reaction. The role of H19 in invasion, angiogenesis, and stemness of glioblastoma cells was then investigated using commercially produced cell lines (U87 and U373). The effects of H19 overexpression on glioblastoma cell invasion and angiogenesis were detected by in vitro Matrigel invasion and endothelial tube formation assay. The effects of H19 on glioblastoma cell stemness and tumorigenicity were investigated by neurosphere formation and an in vivo murine xenograft model. results The authors found that H19 is significantly overexpressed in glioblastoma tissues, and the level of expression was associated with patient survival. In the subsequent investigations, the authors found that overexpression of H19 promotes glioblastoma cell invasion and angiogenesis in vitro. Interestingly, H19 was also significantly overexpressed in CD133 + glioblastoma cells, and overexpression of H19 was associated with increased neurosphere formation of glioblastoma cells. Finally, stable overexpression of H19 was associated with increased tumor growth in the murine xenograft model. coNclusioNs The results of this study suggest that increased expression of H19 lncRNA promotes invasion, angiogenesis, stemness, and tumorigenicity of glioblastoma cells. Taken together, the...

These results suggest that miR-218 sensitizes glioma cells to apoptosis by regulating ECOP-mediated suppression of NF-κB activity, which may provide novel opportunities for glioma therapy.

OBJECTIVE Increased levels of H19 long noncoding RNA (lncRNA) have been observed in many cancers, suggesting that overexpression of H19 may be important in the development of carcinogenesis. However, the role of H19 in human glioblastoma is still unclear. The object of this study was to examine the level of H19 in glioblastoma samples and investigate the role of H19 in glioblastoma carcinogenesis. METHODS Glioblastoma and nontumor brain tissue specimens were obtained from tissue obtained during tumor resection in 30 patients with glioblastoma. The level of H19 lncRNA was detected by real-time quantitative reverse transcription polymerase chain reaction. The role of H19 in invasion, angiogenesis, and stemness of glioblastoma cells was then investigated using commercially produced cell lines (U87 and U373). The effects of H19 overexpression on glioblastoma cell invasion and angiogenesis were detected by in vitro Matrigel invasion and endothelial tube formation assay. The effects of H19 on glioblastoma cell stemness and tumorigenicity were investigated by neurosphere formation and an in vivo murine xenograft model. RESULTS The authors found that H19 is significantly overexpressed in glioblastoma tissues, and the level of expression was associated with patient survival. In the subsequent investigations, the authors found that overexpression of H19 promotes glioblastoma cell invasion and angiogenesis in vitro. Interestingly, H19 was also significantly overexpressed in CD133 glioblastoma cells, and overexpression of H19 was associated with increased neurosphere formation of glioblastoma cells. Finally, stable overexpression of H19 was associated with increased tumor growth in the murine xenograft model. CONCLUSIONS The results of this study suggest that increased expression of H19 lncRNA promotes invasion, angiogenesis, stemness, and tumorigenicity of glioblastoma cells. Taken together, these findings indicate that H19 plays an important role in tumorigenicity and stemness of glioblastoma and thus could be a therapeutic target for treatment of glioblastoma in the future.

This study was aimed to investigate the effect of NF-κB activity on the seizure susceptibility, brain damage, and P-gp expression in kainic acid- (KA-) induced seizure rats. Male SD rats were divided into saline control group (NS group), KA induced epilepsy group (EP group), and epilepsy group intervened with NF-κB inhibitor-pyrrolidine dithiocarbamate salt (PDTC group) or with dexamethasone (DEX group). No seizures were observed in the rats of NS group. Compared with NS group, increased P-gp expression and NF-κB activation in the rat brain of the EP group were observed after KA micro-injection. Both PDTC and DEX pre-treatment significantly increased the latency to grade III or V seizure onset compared to EP group but failed to show neuron-protective effect as the number of survival neurons didn't significantly differ from that in EP group. Furthermore, PDTC pre-treatment significantly decreased P-gp expression along with NF-κB activation in the hippocampus CA3 area and amygdala complex of rats compared with the EP group, implying that NF-κB activation involved in the seizure susceptibility and seizure induced brain P-gp over-expression. Additionally, DEX pre-treatment only decreased P-gp expression level without inhibition of NF-κB activation, suggesting NF-κB independent pathway may also participate in regulating seizure induced P-gp over-expression.

Background: The function of microRNA-542-3p (miR-542-3p) in rat epilepsy is still unclear. Methods: The levels of miR-542-3p and toll-like receptor 4 (TLR4) were determined through quantitative real-time PCR. The protein levels were examined via the western blot analysis. The relationship between miR-542-3p and TLR4 was confirmed through luciferase assay. Pathological changes were analyzed via Hematoxylin-eosin (HE) and Nissl staining. Results: The rats and hippocampal cells were treated with kainic acid (KA) in vivo and in vitro. miR-542-3p was low in KA-treated rats, hippocampal cells and cerebrospinal fluid of patients with epilepsy. Further functional analysis showed that miR-542-3p overexpression inhibited KAinduced average seizure frequency, damage of hippocampal neuron and cell apoptosis, leading to the alleviation of the brain injury in epilepsy rats. miR-542-3p was determined to downregulate TLR4 expression. The relationship between miR-542-3p and TLR4 was confirmed. TLR4 knockdown reduced KA-induced nuclear factor-kappa B p65 (NF-κB p65), multidrug resistance 1 (MDR1), P-glycoprotein (P-gp) and apoptosis-associated protein levels. Further, for NF-κB p65, MDR1, P-gp and apoptosis-associated protein levels detection, miR-542-3p mimic showed a suppressive effect on these KA-induced protein levels, whereas TLR4 overexpression ameliorated the miR-542-3p-induced these protein levels in KA-treated epilepsy rats. Conclusion: We identified that miR-542-3p attenuated seizure-induced brain injury and the expression of P-gp in epilepsy rats through inhibiting TLR4/NF-κB signaling pathway, which might contribute to improved epilepsy therapy.