Identification of TMEM159 as a biomarker of glioblastoma progression based on immune characteristics

Background:Glioblastoma multiforme(GBM)is the most general malignancy of the primary central nervous system that is characterized by high aggressiveness and lethality.Transmembrane protein 159(TMEM159)is an endoplasmic reticulum protein that can form oligomers with seipin.The TMEM159-seipin complex decides the site of lipid droplet(LD)formation,and the formation of LDs is a marker of GBM.However,the role of TMEM159 in the progression of GBM has not been investigated to date.Methods:In this study,we examined the genes that may be associated with patient prognosis in GBM by bioinformatics analyses,and identified the key genes that affect the development of GBM using single-cell RNA sequencing technology.The biological functions of TMEM159 in GBM cells were additionally assessed by clone formation and transwell assays as well as using a model of chick embryo chorioallantois membrane(CAM)and western blotting.The association between TMEM159 and epidermal growth factor receptor(EGFR)was finally analyzed in GBM cells.Results:A prognostic model was established and validated for predicting the prognosis.Survival curve analysis showed a critical difference in the prognosis of the high-and low-risk groups predicted by the prognostic model.The results demonstrated that TMEM159 affected the proliferation and invasion of GBM cells.The chick embryo CAM assays demonstrated that the inhibition of TMEM159 expression reduced angiogenesis in the CAM model.Conclusions:The prognostic model achieved good predictive potential for high-risk patients.The findings also revealed that TMEM159 might be an important prognostic factor for GBM,indicating that the protein may be a promising therapeutic target for suppressing the development of GBM.

The antitumor effects of Newcastle disease virus on glioma

Glioma is the most common primary malignant brain tumor with a poor survival rate.In recent years,no significant progress has been made in the treatment of gliomas in contrast to the development of improved diagnosis via molecular typing.Newcastle disease virus(NDV),a negative-stranded RNA virus that exhibits oncolytic activity,has been investigated for its capacity to elicit antitumor activity in many types of cancers,including glioma.Therefore,application of oncolytic viruses,such as NDV,as a new treatment strategy to specifically target aberrant signaling in glioblastomas has brought new hope.For many years,NDV has been investigated for its in vivo and in vitro efficacy in the treatment of various tumor cells.Based on its safety in humans,specificity for tumor cells,and immunostimulatory properties,NDV represents a promising antitumor agent.In this review,we summarize the background of NDV and the antitumor mechanisms of NDV-mediated oncolysis,discuss the potential value and role of NDV in gliomas,and describe new advances and perspectives for future research.

Nuclear Aurora kinase A triggers programmed death-ligand 1-mediated immune suppression by activating MYC transcription in triple-negative breast cancer

Background:Increasing studies have reported that oncogenes regulate components of the immune system,suggesting that this is a mechanism for tumorigenesis.Aurora kinase A(AURKA),a serine/threonine kinase,is involved in cell mitosis and is essential for tumor cell proliferation,metastasis,and drug resistance.However,the mechanism by which AURKA is involved in immune response regulation is unclear.Therefore,this study aimed to investigate the role of AURKA in immune regulation in triple-negative breast cancer(TNBC).Methods:Peripheral blood mononuclear cells(PBMCs)were co-cultured with TNBC cells.The xCELLigence Real-Time Cell Analyzer-MP system was used to detect the killing efficiency of immune cells on TNBC cells.The expression of immune effector molecules was tested by quantitative real-time polymerase chain reaction(qRT-PCR)to evaluate immune function.Furthermore,to validate AURKA-regulated immune response in vivo,4T1 murine breast cancer cell line with AURKA overexpression or downregulation was engrafted into BALB/c mice.The distribution and proportion of immune cells in tumors were further evaluated by immunohistochemistry and flow cytometry.Results:Downregulation of AURKA in TNBC cells increased immune response by activating CD8^(+)T cell proliferation and activity.Nuclear rather than cytoplasmic AURKA-derived programmed death-ligand 1(PD-L1)expression was independent of its kinase activity.Mechanistic investigations showed that nuclear AURKA increased PD-L1 expression via an MYC-dependent pathway.PD-L1 overexpression mostly reversed AURKA silencing-induced expression of immune effector molecules,including interleukin-(IL-2),interferon-γ(IFN-γ),and perforin.Moreover,AURKA expression was negatively correlated with the enrichment and activity of tumor-infiltrating CD8^(+)T cells in 4T1 engrafted BALB/c mouse model.Conclusions:Nuclear AURKA elevated PD-L1 expression via an MYCdependent pathway and contributed to immune evasion in TNBC.Therapies targeting nuclear AURKA may restore immune responses against tumors.