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DLGAP5 promotes progression of oral squamous cell carcinoma by regulating the Warburg effect
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Qingzi ZHANG1, 2, Foqing GUO1, Yongqin CHEN1, 2, Feifei XIA1, Jun LUO1, 2, Zhe LIU3, Xiaoyu ZHA1, Changxue LI1
Journal of Army Medical University | 2025, 47(22) : 2749 - 2762
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Journal of Army Medical University | 2025, 47(22): 2749-2762
• Basic Medicine •
DLGAP5 promotes progression of oral squamous cell carcinoma by regulating the Warburg effect
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Qingzi ZHANG1, 2, Foqing GUO1, Yongqin CHEN1, 2, Feifei XIA1, Jun LUO1, 2, Zhe LIU3, Xiaoyu ZHA1, Changxue LI1
Affiliations
  • 1Department of Oral and Maxillofacial Surgery,the First Affiliated Hospital of Shihezi University,Shihezi,Xinjiang
  • 2School of Medicine,Shihezi University,Shihezi,Xinjiang
  • 3Department of Oral and Maxillofacial Surgery,Jinan Third People’s Hospital,Jinan,Shandong,China
Published: 2025-11-30 doi: 10.16016/j.2097-0927.202509067
Outline
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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.

oral squamous cell carcinoma  /  discs large homolog associated protein 5  /  Warburg effect  /  hexokinase 2  /  enolase 1
张晴子, 郭佛清, 陈永琴, 夏飞飞, 骆骏, 刘喆, 查小雨, 黎昌学. DLGAP5通过调控Warburg效应促进口腔鳞状细胞癌的进展. 陆军军医大学学报, 2025 , 47 (22) : 2749 -2762 . DOI: 10.16016/j.2097-0927.202509067
Qingzi ZHANG, Foqing GUO, Yongqin CHEN, Feifei XIA, Jun LUO, Zhe LIU, Xiaoyu ZHA, Changxue LI. DLGAP5 promotes progression of oral squamous cell carcinoma by regulating the Warburg effect[J]. Journal of Army Medical University, 2025 , 47 (22) : 2749 -2762 . DOI: 10.16016/j.2097-0927.202509067
Year 2025 volume 47 Issue 22
12
4
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Article Info
doi: 10.16016/j.2097-0927.202509067
  • Receive Date:2025-09-19
  • Online Date:2026-10-30
  • Published:2025-11-30
Article Data
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History
  • Received:2025-09-19
  • Revised:2025-10-30
Affiliations
    1Department of Oral and Maxillofacial Surgery,the First Affiliated Hospital of Shihezi University,Shihezi,Xinjiang
    2School of Medicine,Shihezi University,Shihezi,Xinjiang
    3Department of Oral and Maxillofacial Surgery,Jinan Third People’s Hospital,Jinan,Shandong,China
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表12种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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