LncRNA HLA-F-AS1 Enhances the Migration, Invasion and Apoptosis of Glioblastoma Cells by Targeting lncRNA MEG3.

BACKGROUND: Previous studies revealed the oncogenic role of long non-coding RNA (lncRNA) HLA-F-AS1 in colon cancer and breast cancer, while its role in other cancers is unclear. We predicted the direct interaction between HLA-F-AS1 and MEG3, which is a tumor suppressor lncRNA. We then assessed the interaction between HLA-F-AS1 and MEG3 in glioblastoma (GBM). METHODS: The expression levels of HLA-F-AS1 and MEG3 in GBM and paired non-tumor tissues from 60 GBM patients were analyzed by RT-qPCR. Overexpression of HLA-F-AS1 and MEG3 was achieved in GBM cells to explore the interaction between them. The direct interaction between them was confirmed by RNA pull-down assay. The roles of HLA-F-AS1 and MEG3 in cell invasion, migration and apoptosis were explored by Transwell assays and cell apoptosis assay. RESULTS: HLA-F-AS1 was highly expressed, and MEG3 was downregulated in GBM. Overexpression of HLA-F-AS1 reduced the expression levels of MEG3 while overexpression of MEG3 did not alter the expression of HLA-F-AS1. HLA-F-AS1 increased cell migration and invasion, but decreased cell apoptosis. MEG3 played opposite roles and reduced the effects of HLA-F-AS1 on cell behaviors. CONCLUSION: HLA-F-AS1 may sponge MEG3 in GBM cells to promote cell invasion and migration, and to suppress cell apoptosis.

Long non-coding RNA as a potential biomarker for prognosis of glioma: A protocol for systematic review and meta-analysis.

BACKGROUND: The molecular mechanism of Glioma is still unclear, and there are few early diagnostic markers. Therefore, it is urgent to figure out effective preventive measures, active diagnostic methods and rapid treatment measures. In recent years, relevant studies have revealed that long non-coding RNA (lncRNA) is associated with the prognosis of Glioma. However, these results have not been supported by any evidence. Therefore, this study carried out a meta-analysis method to analyze the relationship between lncRNA and the prognosis of Glioma. In addition, bioinformatics analysis was conducted to investigate the mechanism and related pathways of lncRNAs in Glioma. METHODS: We performed a systematic search in electronic databases, including China National Knowledge Infrastructure, Chinese Biomedical literature Database, Chinese Scientific and Journal Database, Wan Fang database, PubMed, EMBASE, Cochrane Library and Web of Science, to investigate the potential association between lncRNA expression and prognostic significance and clinical features in glioma patients. Hazards ratios (HRs) with corresponding 95% confidence intervals (CIs) were pooled to estimate the prognosis value of lncRNA by Stata16.0 software. The online tool AnnoLnc was applied to screen the co-expressed gene related to each lncRNA, David was used for gene ontology (GO) analysis and enrichment analysis of the signal pathway, and through Starbase, the possible competitive endogenous RNA network of lncRNAs was constructed. RESULTS: The results of this meta-analysis would be submitted to peer-reviewed journals for publication. CONCLUSION: This study will provide evidence-based medical evidence for lncRNA, so as to predict the prognosis of Glioma and bioinformatics analysis will provide ideas for the mechanism study on Glioma.

Tissue distribution study of periplocin and its two metabolites in rats by a validated LC-MS/MS method.

Periplocin is a cardiac glycoside and has been used widely in the clinic for its cardiotonic, anti-inflammatory and anti-tumor effects. Although it is taken frequently by oral administration in the clinic, there have been no reports demonstrating that periplocin could be detected in vivo after an oral administration, so there is an urgen need to determine the characteristics of periplocin in vivo after oral administration. In this study, a sensitive and reliable liquid chromatography-tandem mass spectrometry method was developed and validated to identify and quantify periplocin and its two metabolites in rat tissue after a single dosage of perplocin at 50 mg/kg. The results demonstrated that periplocin and its two metabolites were detected in all of the selected tissues; periplocin could reach peak concentration quickly after administration, while periplocymarin and periplogenin reached maximum concentration > 4.83 h after administration. The tissue distribution of analytes tended to be mostly in the liver, and higher analyte concentrations were found in the heart, liver, spleen, lung and kidney, but a small amount of chemical constituents was distributed into the brain. The consequences obtained using this method might provide a meaningful insight for clinical investigations and applications.

Treponema pallidum flagellin FlaA2 induces IL-6 secretion in THP-1 cells via the Toll-like receptor 2 signaling pathway.

Treponema pallidum subsp. pallidum membrane proteins are considered as potent inducers in the initiation and development of inflammation. In the present study, the mechanism that leads to the production of interleukin 6 (IL-6), one of the key proinflammatory cytokines, by human monocytic THP-1 cells when these cells are treated with T. pallidum flagellin FlaA2 was investigated. Stimulation with flagellin FlaA2 can induce IL-6 expression in human monocytes and augment the phosphorylation of ERK, p38, and NF-κB, but has no effect on the phosphorylation of JNK. Likewise, FlaA2-induced IL-6 production was found to be attenuated by inhibitors for ERK, p38, and NF-κB, but not by JNK inhibitor. Immunofluorescence analysis showed that flagellin FlaA2 could stimulate the translocation of IκBα from the cytosol to the nucleus, and this phenomenon could be inhibited by the specific inhibitor BAY11-7082. FlaA2-induced IL-6 expression was also proved to be abrogated by transfection with dominant negative (DN) plasmid of MyD88. We further demonstrated that transfection with DN-TLR2 was sufficient to attenuate IL-6 expression and the phosphorylation of ERK, p38, and IκBα. These results suggest that flagellin FlaA2 induces IL-6 production via signaling pathways involving TLR2, MyD88, ERK, p38, and NF-κB in monocytes, which could contribute to the pathogenesis of T. pallidum.

Structure-activity relationship study of anticancer thymidine-quinoxaline conjugates under the low radiance of long wavelength ultraviolet light for photodynamic therapy.

Thymidine quinoxaline conjugate (dT-QX) is a thymidine analog with selective cytotoxicity against different cancer cells. In this study, the structure activity relationship study of dT-QX analogs was carried out under the low radiance of black fluorescent (UVA-1) light. Significantly enhanced cytotoxicity was observed under UVA-1 activation among analogs containing both thymidine and quinoxaline moieties with different length of the linker, stereochemical configuration and halogenated substituents. Among these analogs, the thymidine dichloroquinoxaline conjugate exhibited potent activity under UVA-1 activation as the best candidate with EC50 at 0.67 µM and 1.3 µM against liver and pancreatic cancer cells, respectively. In contrast, the replacement of thymidine moiety with a galactosyl residue or the replacement of quinoxaline moiety with a fluorescent pyrenyl residue or a simplified diketone structure resulted in the full loss of activity. Furthermore, it was revealed that the low radiance of UVA-1 at 3 mW/cm(2) for 20 min was sufficient enough to induce the full cytotoxicity of thymidine dichloroquinoxaline conjugate and that the cytotoxic mechanism was achieved through a rapid and steady production of reactive oxygen species.