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        Phosphofructokinase 1 platelet isoform induces PD-L1 expression to promote glioblastoma immune evasion

        Wang Silu,Park Su Hwan,임제선,Park Yun-Yong,Du Linyong,Lee Jong-Ho 한국유전학회 2022 Genes & Genomics Vol.44 No.12

        Background: Overexpression of PD-L1 is observed in many types of human cancer, including glioblastoma (GBM) and contributes to tumor immune evasion. In addition, GBM shows highly-activated aerobic glycolysis due to overexpression of phosphofructokinase 1 platelet isoform (PFKP), which the key enzyme in the glycolysis. However, it remains unclear whether the metabolic enzyme PFKP plays a role in the regulation of PD-L1 expression and GBM immune evasion. Objective: We aimed to investigate the non-metabolic role of PFKP in PD-L1 expression-induced GBM immune evasion. Methods: The mechanisms of PFKP-induced PD-L1 expression were studied by several experiments, including real-time PCR, immunoblot analysis, and ATP production. The coculture experiments using GBM cell and T cells were performed to evaluate the effect of PFKP on T cell activation. The clinical relationship between PFKP and PD-L1 was analyzed in The Cancer Genome Atlas (TCGA) database and in human GBM specimens. Results: We showed that PFKP promotes EGFR activation-induced PD-L1 expression in human GBM cells. Importantly, we demonstrated that EGFR-phosphorylated PFKP Y64 plays an important role in AKT-mediated β-catenin transactivation and subsequent PD-L1 transcriptional expression, thereby enhancing the GBM immune evasion. In addition, based on our findings, the levels of PFKP Y64 phosphorylation are positively correlated with PD-L1 expression in human GBM specimens, highlighting the clinical significance of PFKP Y64 phosphorylation in the GBM immune evasion. Conclusion: These findings provide new mechanistic insight into the regulation of PD-L1 expression by a non-metabolic function of PFKP on tumor cells.

      • KCI등재

        Hemicastration induced spermatogenesis-related DNA methylation and gene expression changes in mice testis

        Yixin Wang,Long Jin,Jideng Ma,Li Chen,Yuhua Fu,Keren Long,Silu Hu,Yang Song,Dazhi Shang,Qianzi Tang,Xun Wang,Xuewei Li,Mingzhou Li 아세아·태평양축산학회 2018 Animal Bioscience Vol.31 No.2

        Objective: Hemicastration is a unilateral orchiectomy to remove an injured testis, which can induce hormonal changes and compensatory hypertrophy of the remaining testis, and may influence spermatogenesis. However, the underlying molecular mechanisms are poorly understood. Here, we investigated the impact of hemicastration on remaining testicular function. Methods: Prepubertal mice (age 24 days) were hemicastrated, and their growth was monitored until they reached physical maturity (age 72 days). Subsequently, we determined testis DNA methylation patterns using reduced representation bisulfite sequencing of normal and hemicastrated mice. Moreover, we profiled the testicular gene expression patterns by RNA sequencing (RNA-seq) to examine whether methylation changes affected gene expression in hemicastrated mice. Results: Hemicastration did not significantly affect growth or testosterone (p>0.05) compared with control. The genome-wide DNA methylation pattern of remaining testis suggested that substantial genes harbored differentially methylated regions (1,139) in gene bodies, which were enriched in process of protein binding and cell adhesion. Moreover, RNA-seq results indicated that 46 differentially expressed genes (DEGs) involved in meiotic cell cycle, synaptonemal complex assembly and spermatogenesis were upregulated in the hemicastration group, while 197 DEGs were downregulated, which were related to arachidonic acid metabolism. Integrative analysis revealed that proteasome 26S subunit ATPase 3 interacting protein gene, which encodes a protein crucial for homologous recombination in spermatocytes, exhibited promoter hypomethylation and higher expression level in hemicastrated mice. Conclusion: Global profiling of DNA methylation and gene expression demonstrated that hemicastration-induced compensatory response maintained normal growth and testicular morphological structure in mice.

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        STYXL1 promotes proliferation and epithelial mesenchymal transition of gastric cancer cells via activating the PI3K/AKT pathway

        Chen Silu,Yu Weiyan,Li Ziyue,Wang Yadong,Peng Bo 대한독성 유전단백체 학회 2024 Molecular & cellular toxicology Vol.20 No.2

        Background Gastric cancer (GC) is a common and grievous disorder with high heterogeneity. Serine/threonine/tyrosine-interacting-like protein 1 (STYXL1), a pseudophosphatase without catalytic activity, plays a important roles in cellular pathways and various cancers. However, its role and mechanism in GC remain unclear. Objectives This study aimed to explore the role and possible mechanism of STYXL1 in GC cells. Results The results showed that STYXL1 expression was elevated in GC. Both loss- and gain-of-function results showed that STYXL1 enhanced cell viability, colony formation, cell invasion and migration, and the protein expression of BCL-2 and Vimentin, but reduced the apoptosis rate and the protein level of BAX, cleaved caspase 3 and E-Cadherin in vitro. Mechanically, the levels of p-PI3K/PI3K and p-AKT/AKT were observably elevated by overexpression of STYXL1, and markedly reduced by silencing of STYXL1 in both SNU-1 and HGC-27 cells. Conclusion STYXL1 promoted cell growth, migration, invasion and EMT with decreased apoptosis, which was closely related with the activation of PI3K/AKT pathway in GC.

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        Antibacterial Graphene Oxide/Chitosan Composite Compression Garment Fabric

        Lihuan Zhao,Siyu Zhang,Yuwen Wang,Jun Li,Yanyan Li,Yujie Yang,Silu Liu 한국섬유공학회 2022 Fibers and polymers Vol.23 No.7

        To solve issues related to hypertrophic scars, such as the risk of bacterial infections, due to the wearing ofcompression garments for extended periods of time, we prepared an antibacterial compression garment fabric (CGF) with agraphene oxide (GO)/chitosan (CS) composite. First, the GO/CS composite was prepared and used as an antibacterial agentfor antibacterial finishing of the CGF. Then, silane coupling agent γ-(methacryloxy) propyl trimethoxysilane (KH570) wasused to modify the GO/CS-finished CGF to improve the washing fastness properties of the antibacterial fabric. Finally, thedurability, physical properties, and biological safety of the antibacterial finished fabrics were studied. We found that the GO/CS composite was successfully synthesized, and the antibacterial finished fabrics were endowed with antibacterial activityagainst both gram-negative bacteria Esherichia coli (E. coli, AATCC 6538) and gram-positive bacteria Staphylococcusaureus (S. aureus, AATCC 25922), with bacteriostatic rates of 92.09 % and 99.33 %, respectively. Moreover, the durability ofthe finished fabric was effectively improved by KH570 treatment. One disadvantage was that the comfort of the antibacterialfinished fabric was affected to a certain extent; however, biological experiments showed that the CGF finished by GO/CS/KH570 showed no potential cytotoxicity on the human body and did not cause skin irritation. The prepared antibacterialfinished CGF based on the GO/CS/KH570 composite could effectively reduce the bacterial infection rates of patients wearingcompression garments, which could significantly alleviate patient suffering.

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