1.DLGAP5 promotes progression of oral squamous cell carcinoma by regulating the Warburg effect
Qingzi ZHANG ; Foqing GUO ; Yongqin CHEN ; Feifei XIA ; Jun LUO ; Zhe LIU ; Xiaoyu ZHA ; Changxue LI
Journal of Army Medical University 2025;47(22):2749-2762
Objective Investigate the expression level of discs large homolog associated protein 5(DLGAP5)in oral squamous cell carcinoma(OSCC)and analyze its effects on cell proliferation,migration,invasion capacity,and the Warburg effect.Methods Bioinformatics analysis was performed to identify the potential therapeutic targets for OSCC.A total of 72 OSCC tissue samples and 40 adjacent non-cancerous tissue samples collected in the First Affiliated Hospital of Shihezi University from 2013 to 2024 were included,and the clinical pathological and prognostic data were collected from patients.Immunohistochemistry assay was applied to detect the protein expression of DLGAP5,and its association with clinical pathological features was analyzed.Kaplan-Meier survival curve was plotted for survival analysis,and Cox regression model was employed to analyze the prognostic factors.The expression of DLGAP5 at mRNA and protein levels was detected in HOK,SCC-9,SCC-15,SCC-25,and CAL-27 cell lines with RT-qPCR and Western blotting,respectively.Four small interfering RNAs(siRNAs)were designed to target the DLGAP5 sequence,and then based on the transfection efficiency,the sequence with optimal silencing effect was selected for subsequent functional studies.After DLGAP5 was silenced in the CAL-27 and SCC-15 cells,Western blotting was applied to detect the expression of hexokinase 2(HK2)and enolase 1(ENO1),CCK-8,scratch healing and Transwell assays were conducted to assess cell proliferation,migration,and invasion capabilities,and glucose,lactate,and ATP detection kits were utilized to determine the glycolytic metabolic levels in OSCC cells.Results Bioinformatics analysis indicates that DLGAP5 is a potential key therapeutic target for OSCC.Experimental validation demonstrated that DLGAP5 was highly expressed in both OSCC tissues and cells(P<0.05).Analysis of clinical pathology and prognostic data revealed that DLGAP5 expression level was significantly correlated with tumor TNM stage,lymph node metastasis,and differentiation grade in OSCC patients,and high DLGAP5 expression was associated with poor prognosis(P<0.05).DLGAP5 silencing resulted in significantly reduced expression of HK2 and ENO1,markedly decreased levels of glycolytic metabolites(P<0.05),and notably declined cell proliferation,migration,and invasion capabilities(P<0.05).Conclusion DLGAP5 is highly expressed in OSCC.Silencing DLGAP5 may inhibit OSCC cell proliferation,migration,and invasion by indirectly regulating the Warburg effect,and the molecule is associated with poor prognosis in the OSCC patients.
2.Effect of hydrogen sulfide on airway inflammation induced by ozone in mice
Yubo ZHOU ; Zhaodi FU ; Lifen ZHOU ; Qingzi CHEN ; Chuntao YANG ; Jianhua LI
Chinese Journal of Pathophysiology 2016;32(10):1837-1842
[ ABSTRACT] AIM:To investigate the effect of hydrogen sulfide ( H2 S) on airway inflammation induced by ozone (O3) exposure and its mechanisms.METHODS:C57BL/6 mice (n=32) were randomly divided into control group, O3 group, NaHS+O3 group and NaHS group.The mice in O3 group and O3 +NaHS group were exposed to 2.14 mg/m3 O3 for 3 h on days 1, 3 and 5, while the mice in control group and NaHS group were exposed to filtered air .NaHS (14μmol/kg) was administered intraperitoneally to the mice in NaHS group and O 3 +NaHS group 30 min before each exposure .After the last exposure for 24 h, the airway responsiveness was determined , and bronchoalveolar lavage fluid ( BALF) was collected for counting inflammatory cells and measuring total protein concentration .The lung tissues were collected for observing the morphological changes with HE staining .The levels of interleukin-6 ( IL-6 ) , interleukin-8 ( IL-8 ) , malondialdehyde ( MDA) and NF-κB p65 protein in the lungs were determined .RESULTS: Compared with control group , the airway re-sponsiveness, inflammatory cells, protein concentration, inflammation score, levels of IL-6, IL-8, MDA and NF-κB p65 in O3 group increased significantly , but these in NaHS+O3 group decreased compared with O 3 group.CONCLUSION: The present findings suggest that H 2 S attenuates O3 induced airway inflammation by inhibiting NF-κB expression and preventing lipid peroxidation .

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