Background To explore the mechanism of LINC00470 in serum exosomes from glioma patients regulating the autophagy and proliferation of glioma cells. Methods Exosomes were extracted from glioma patients (GBM-exo). Expression of LINC00470 in exosomes was analyzed with the clinicopathological characteristics of glioma patients. Glioma mouse model was established. The effects of LINC00470, miR-580-3p and WEE1 on cell autophagy and proliferation, as well as the activation of PI3K/AKT/mTOR pathway were measured. Dual luciferase reporter assay and RNA immunoprecipitation (RIP) were conducted to validate the binding of LINC00470 and miR-580-3p and of miR-580-3p and WEE1. Results LINC00470 overexpressed in GBM-exo and associated with disease severity and postoperative survival time of glioma patients. GBM-exo deteriorated tumor progression in nude mice. Cells incubated with GBM-exo or transfected with pcDNA3.1-LINC00470/miR-580-3p inhibitor/pcDNA3.1-WEE1 had less autophagosome, downregulated LC3-II/LC3-I and Beclin1 expression levels and increased expression of p62 as well as strengthened proliferation ability. The PI3K/AKT/mTOR pathway was activated. LINC00470 competitively bound to miR-580-3p with WEE1. Conclusion LINC00470 in GBM-exo can bind to miR-580-3p in glioma cells to regulate WEE1 expression and activate the PI3K/AKT/mTOR pathway, thereby inhibiting autophagy and enhancing the proliferation of glioma cells.

Overexpression of Tafazzin (TAZ), a mitochondrial protein, is often observed in many cancers. However, the association between aberrant expression of TAZ and drug resistance remains unclear. The aim of this study is to explore the role of TAZ in regulating the TRAIL resistance in glioma. We thus established the TRAIL resistance models on glioma by using the U87 and U251 cell lines (U87/R and U251/R). As the results, obvious overexpression of TAZ was observed in U87/R and U251/R cells. However, knockdown of TAZ increased the sensitivity of U87/R and U251/R cells to TRAIL-induced apoptosis. By contrast, expression of miR-125b was downregulated in U87/R and U251/R cells compared to the parental U87 and U251 cells. Furthermore, decrease of miR-125b was responsible for overexpression of TAZ, because the results of dual-luciferase reporter assays verified that TAZ was targeted by miR-125b. We then showed that enforced expression of miR-125b resensitized the U87/R and U251/R cells to TRAIL-dependent damage of mitochondria and activation of caspase-9 and -3. We demonstrated that overexpression of TAZ caused by downregulation of miR-125b promoted resistance of glioma cells to TRAIL. MiR-125b/TAZ axis may represent a potential strategy to reverse the TRAIL in glioma.

Sepsis-induced acute lung injury (ALI) culminates in multiple organ failure via uncontrolled inflammatory responses and requires effective treatment. Herein, we aimed to investigate the effect of calycosin (CA), a natural isoflavonoid, on sepsis-induced ALI. CA attenuated lipopolysaccharide (LPS) and cecal ligation and puncture (CLP)-induced structural damage and inflammatory cell infiltration in lung tissues by histopathological analysis. CA significantly reduced lung wet/dry ratio, inflammatory cell infiltration in bronchoalveolar lavage fluid, and myeloperoxidase activity. Moreover, CA improved the survival of septic mice. CA also substantially inhibited interleukin (IL)-1β and IL-18 levels and cleaved caspase 1 expression and activity in lung tissues. Additionally, CA markedly suppressed oxidative stress by increasing levels of superoxide dismutase and glutathione while decreasing malondialdehyde. In vitro assay showed that CA significantly inhibited LPS-induced IL-1β and IL-18 levels and cleaved caspase 1 expression and activity in BMDMs. Moreover, CA blocked the interaction among NLRP3, ASC, and caspase 1 in LPS-treated cells. CA markedly reduced mitochondrial ROS levels. Significantly, compared with CA treatment, the combination of CA and MitoTEMPO (mitochondria-targeted antioxidant) did not further reduce the IL-1β and IL-18 levels and cleaved caspase 1 expression and activity and decreased mitochondrial ROS levels. Collectively, the inhibition of mitochondrial ROS-mediated NLRP3 inflammasome activation contributes to the protective effects of CA, which may be considered a potential therapeutic agent for septic ALI.