Background: Glioma is the most common malignant tumor of the central nervous system, with high heterogeneity, strong invasiveness, high therapeutic resistance, and poor prognosis, comprehending a serious challenge in neuro-oncology. Until now, the mechanisms underlying glioma progression have not been fully elucidated. Methods:The expression of DExH-box helicase 9 (DHX9) in tissues and cells was detected by qRT-PCR and western blot. EdU and transwell assays were conducted to assess the effect of DHX9 on proliferation, migration and invasion of glioma cells.Cocultured model was used to evaluate the role of DHX9 on macrophages recruitment and polarization. Animal study was performed to explore the role of DHX9 on macrophages recruitment and polarization in vivo. Bioinformatics analysis, dualluciferase reporter assay and chromatin immunoprecipitation (ChIP)-qPCR assay was used to explore the relation between DHX9 and TCF12/CSF1.Results: DHX9 was elevated in gliomas, especially in glioblastoma multiforme (GBM).Besides promoting the proliferation, migration, and invasion of glioma cells, DHX9 facilitated the infiltration of macrophages into glioma tissues and polarization to M2-like macrophages, known as tumor-associated macrophages (TAMs). DHX9 silencing decreased the expression of colony-stimulating factor 1 (CSF1), which partially restored the inhibitory effect on malignant progress of glioma and infiltration of TAMs caused by DHX9 knockdown by targeting the transcription factor 12 (TCF12). Moreover, TCF12 could directly bind to the promoter region of CSF1. Conclusion: DHX9/TCF12/CSF1 axis regulated the increases in the infiltration ofTAMs to promote glioma progression and might be a novel potential target for future immune therapies against gliomas.
Background The recent development of dendritic cell (DC)‐based immunotherapy has resulted in advances in glioblastoma multiforme (GBM) treatment. However, the cell fate of DCs in the GBM microenvironment, especially in microenvironments in which glioma stem cell (GSCs)‐mediated remodeling has resulted in highly immunosuppressive conditions, has not yet been fully investigated. Methods Observed the interaction between GSCs and primary cultured DCs in a dual‐color tracing model, monoclonal and continuously passaged highly proliferative DCs, and named transformed DCs (t‐DCs). The expression of DC‐specific surface markers was analyzed using RT‐PCR, chromosome karyotype, and flow cytometry. The expression of long pentraxin 3 (PTX3) and its transcription factor zinc finger protein 148 (ZNF148) in t‐DCs was detected using qRT‐PCR and western blot. CCK8 and transwell assays were conducted to assess the effect of ZNF148 and PTX3 on the proliferation, migration, and invasion of t‐DCs. Bioinformatics analysis, dual‐luciferase reporter assay, and chromatin immunoprecipitation (ChIP)‐qPCR assay were used to explore the relation between ZNF148 and PTX3. Results Transformed DCs (t‐DCs) still expressed DC‐specific surface markers, namely, CD80 and CD11c, and immune‐related costimulatory molecules, namely, CD80, CD86, CD40, and ICAM‐1. However, the expression levels of these molecules in t‐DCs decreased moderately compared to those in naive DCs. Stable overexpression of PTX3 further promoted the proliferation and migration of t‐DCs in vitro, decreased the expression of costimulatory molecules, and increased the tumorigenicity of t‐DCs in vivo. The transcription factor zinc finger protein 148 (ZNF148) was directly bound to the PTX3 promoter region and enhanced PTX3 expression. Downregulation of ZNF148 significantly decreased PTX3 expression and reduced the proliferation and migration of t‐DCs. Overexpression of ZNF148 significantly increased PTX3 expression and promoted the proliferation and migration of t‐DCs, achieving the same biological effects as PTX3 overexpression in t‐DCs. Simultaneously, the downregulation of ZNF148 partially reversed the effect of PTX3 overexpression in t‐DCs. Conclusion The ZNF148/PTX3 axis played an important role in regulating the malignant transformation of DCs after cross‐talk with GSCs, and this axis may serve as a new target for sensitizing GBM to DC‐based immunotherapy.
Many organizations are willing to increase human capital investment through various employee training programs. This study empirically examines a proposed model that explains the relationship between the different types of employee training, including general and firm-specific training and employee turnover in Korean firms. This study used a survey sample of 10,069 employees in 467 publicly traded firms in South Korea. 78% of participating companies provided training programs to the employees. This study conducted quantitative cross-sectional regression analyses to test the hypotheses. The study suggests empirical evidence that general training and firm-specific training reduce employee turnover intention. Moreover, the magnitude of firm-specific training on turnover intention is much higher than general training. Furthermore, employee organizational identification has a partial mediating effect on training and turnover intention. However, the study found no substantial evidence of the moderating effect of employees’ justice perception of receiving training opportunities. Based on the human capital theory and social exchange perspective, the results indicate that both types of training programs help employee retention, and cultivating employee organizational identification can be critical in the training-turnover process.
AimExosomal miRNAs derived from glioblastoma stem cells (GSCs) are important mediators of immunosuppressive microenvironment formation in glioblastoma multiform (GBM), especially in M2‐like polarization of tumor‐associated macrophages (TAMs). However, the exact mechanisms by which GSCs‐derived exosomes (GSCs‐exo) facilitate the remodeling of the immunosuppressive microenvironment of GBM have not been elucidated.MethodsTransmission electron microscopy (TME) and nanoparticle tracking analysis (NTA) were applied to verify the existence of GSCs‐derived exosomes. Sphere formation assays, flow cytometry, and tumor xenograft transplantation assays were performed to identify the exact roles of exosomal miR‐6733‐5p. Then, the mechanisms of miR‐6733‐5p and its downstream target gene regulating crosstalk between GSCs cells and M2 macrophages were further investigated.ResultsGSCs‐derived exosomal miR‐6733‐5p induce macrophage M2 polarization of TAMs by positively targeting IGF2BP3 to activate the AKT signaling pathway, which further facilitates the self‐renewal and stemness of GSCs.ConclusionGSCs secrete miR‐6733‐5p‐rich exosomes to induce M2‐like polarization of macrophages, as well as enhance GSCs stemness and promote malignant behaviors of GBM through IGF2BP3 activated AKT pathway. Targeting GSCs exosomal miR‐6733‐5p may provide a potential new strategy against GBM.
Luminogens without recognizable luminophores are attracting increasing attention owing to their particular photophysical properties and outstanding biocompatibility features. Despite the rapid advance, it is still a formidable challenge to synthesize...
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