LncRNA FOXD3-AS1 Contributes to Glioblastoma Progression Via Sponging miR-3918 to Upregulate CCND1.

AIM: To elucidate the pro-tumorigenic role of IncRNA FOXD3-AS1 in glioblastoma. MATERIAL AND METHODS: The expression of miR-3918, FOXD3-AS1, and CCND1 was measured in glioblastoma cells and tissues using reverse transcriptase quantitative PCR (RT-qPCR). The effect of FOXD3-AS1 silencing on the proliferation of glioblastoma cells was assessed in vitro using CCK-8 and colony formation assays and in vivo using xenograft mouse models. Additionally, the expression levels of the apoptosis-related proteins, Bcl-2 and Bax, were assessed using western blotting. Bioinformatic analysis and luciferase reporter assays assisted by RNA immunoprecipitation (RIP) and RNA pull-down experiments were conducted to validate the interactions among FOXD3-AS1, CCND1, and miR-3918. RESULTS: FOXD3-AS1 and CCND1 were highly expressed in glioblastoma tissues and cells, whereas miR-3918 was poorly expressed. The expressions of FOXD3-AS1 and CCND1 were inversely associated with miR-3918 levels in glioblastoma tissues. FOXD3-AS1 silencing weakened the proliferative capacity and accelerated apoptosis of glioblastoma cells in vitro and hampered tumor growth in vivo. Mechanical investigations showed that FOXD3-AS1 knockdown increased miR-3918 expression and inhibited glioblastoma cell growth. Meanwhile, the miR-3918 inhibitor restored CCND1 expression and induced the opposite outcome. CONCLUSION: FOXD3-AS1 facilitates the CCND1-driven progression of glioblastoma by serving as a competing endogenous RNA (ceRNA) for miR-3918. This suggests that FOXD3-AS1 may be a potential therapeutic target for the management of glioblastoma development.

Endoscopic Surgery versus External Ventricular Drainage Surgery for Severe Intraventricular Hemorrhage.

The efficacy and applied value of endoscopic hematoma evacuation vs. external ventricular drainage (EVD) in the treatment of severe ventricular hemorrhage (IVH) were explored and compared. From Jan. 2015 to Dec. 2016, the clinical data of 42 cases of IVH were retrospectively analyzed, including 18 patients undergoing endoscopic hematoma evacuation (group A), and 24 patients receiving EVD (group B). The hematoma clearance rate was calculated by 3D Slicer software, and complications and outcomes were compared between the two groups. There were no significant differences in age, sex and Graeb score between groups A and B (P>0.05). The hematoma clearance rate was 70.81%±27.64% in group A and 48.72%±36.58% in group B with a statistically significant difference (P<0.05). The operative time in groups A and B was 72.45±25.26 min and 28.54±15.27 min, respectively (P<0.05). The Glasgow Coma Scale (GCS) score increased from 9.28±2.72 at baseline to 11.83±2.91 at 1 week postoperatively in group A, and from 8.25±2.62 at baseline to 10.79±4.12 at 1 week postoperatively in group B (P<0.05). The length of hospital stay was 12.67±5.97 days in group A and 17.33±8.91 days in group B with a statistically significant difference (P<0.05). The GOS scores at 6 months after surgery were 3.83±1.12 in group A, and 2.75±1.23 in group B (P<0.05). These results suggested that endoscopic hematoma evacuation has an advantage of a higher hematoma clearance rate, fewer complications and better outcomes in the treatment of severe IVH, indicating it is a safe, effective and promising approach for severe IVH.

Effect of cyclooxygenase­2 inhibition on the development of post­traumatic stress disorder in rats.

Post­traumatic stress disorder (PTSD) is characterized by re­experiencing of a traumatic event, avoidance of trauma­associated stimulation, general changes in mood and cognition, and hyper arousal symptoms. Cyclooxygenase is involved in the production of prostaglandins and thromboxanes, and its inducible form cyclooxygenase­2(COX­2), an important mediator of cell injury in inflammation, is primarily expressed in leukocytes and brain cells. The present study investigated the expression of COX­2 in the hippocampi of rats with PTSD and evaluated the effect of COX­2 inhibition on PTSD. Adult male Wistar rats were randomly divided into three groups: Control (n=20), PTSD (n=20) and intervention group (PTSD+COX­2 inhibitor treatment, n=20). The expression of COX­2 was detected by immunohistochemistry, reverse transcription­quantitative polymerase chain reaction and western blotting. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining was used to observe the apoptosis of rat hippocampal neurons. Tumor necrosis factor α (TNF­α), interleukin (IL)­6 and prostaglandin E2 (PGE2) levels were analyzed by ELISA. Nitric oxide (NO) was detected using the Griess test. The behavioral and cognitive function of rats in the PTSD group was significantly decreased compared with the control group, while the behavioral and cognitive function of rats in the intervention group were improved. The COX­2 mRNA and protein expression levels in hippocampi of rats in the PTSD group were higher than in the control and intervention group. The apoptosis of hippocampus in rats with PTSD was significantly increased compared with the control group and following treatment with COX­2 inhibitor, apoptosis was decreased. In addition, compared with the control group and intervention group, the levels of TNF­α, IL­6, PGE2 and NO in hippocampi of rats were increased in the PTSD group. The present study indicated that COX­2 may be involved in the pathogenesis of PTSD, and inhibition of its expression serves a neuroprotective role in hippocampi of PTSD rats.

Down-regulation of BAG3 inhibits proliferation and promotes apoptosis of glioblastoma multiforme through BAG3/HSP70/HIF-1α signaling pathway.

Bcl2-associated athanogene 3 (BAG3) belongs to the BAG family and regulates many biologic behaviors of tumors. When tumor cells are in a hypoxic condition, BAG3 protein expression level increases, as does HIF-1α which is an important transcription factor induced by hypoxia. Glioblastoma is one of the typical solid tumors existing in a hypoxic microenvironment that can activate expression of BAG3 and HIF-1α. This research aimed to reveal the relationship between BAG3 and HIF-1α and their effects in glioblastoma multiforme. We found that down-regulated BAG3 inhibited proliferation and promoted apoptosis of glioblastoma multiforme U87 and U251 cell lines by decreasing HIF-1α expression level. The mechanism of BAG3 regulating HIF-1α is mainly through increasing degradation of HIF-1α by HSP70. When HIF-1α was up-regulated, induced by HIF-1α plasmid transfection on the basis of down-regulation of BAG3, the proliferation inhibition and apoptosis promotion were partially reversed. This novel result showed, for the first time, that down-regulation of BAG3 resulted in a low expression of HIF-1α under both normoxic or hypoxic conditions and finally caused inhibited proliferation and promoted apoptosis in glioblastoma. The mechanism of down-regulated BAG3 decreased HIF-1α protein expression through enhancing formation of HSP70-HIF-1α complex and promoting degradation of HIF-1α by HSP70.