DLGAP5 promotes progression of oral squamous cell carcinoma by regulating the Warburg effect

ZHANG Qingzi; GUO Foqing; CHEN Yongqin; XIA Feifei; LUO Jun; LIU Zhe; ZHA Xiaoyu; LI Changxue

doi:10.16016/j.2097-0927.202509067

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DLGAP5 promotes progression of oral squamous cell carcinoma by regulating the Warburg effect

Basic Medicine | 更新时间：2025-11-28

- DLGAP5 promotes progression of oral squamous cell carcinoma by regulating the Warburg effect
- Journal of Army Medical University Vol. 47, Issue 22, Pages: 2749-2762(2025)
- 作者机构：
  
  1.石河子大学第一附属医院口腔颌面外科，新疆石河子
  2.石河子大学医学院，新疆石河子
  3.济南市第三人民医院口腔颌面外科，山东济南
- 作者简介：
  
  LI Changxue， E-mail： 3541226598@qq.com
- 基金信息：
  
  Science and Technology Program of XPCC(2023ZD017)
- DOI：10.16016/j.2097-0927.202509067
  CLC： R341;R394.3;R739.85
- Received：19 September 2025，
  
  Revised：2025-10-30，
  
  Accepted：02 November 2025，
  
  Published：30 November 2025
- 稿件说明：
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张晴子，郭佛清，陈永琴，等.DLGAP5通过调控Warburg效应促进口腔鳞状细胞癌的进展［J］.陆军军医大学学报，2025，47（22）：2749-2762.DOI：10.16016/j.2097-0927.202509067.

ZHANG Q Z，GUO F Q，CHEN Y Q，et al.DLGAP5 promotes progression of oral squamous cell carcinoma by regulating the Warburg effect［J］.J Army Med Univ，2025，47（22）：2749-2762.DOI：10.16016/j.2097-0927.202509067.
张晴子，郭佛清，陈永琴，等.DLGAP5通过调控Warburg效应促进口腔鳞状细胞癌的进展［J］.陆军军医大学学报，2025，47（22）：2749-2762.DOI：10.16016/j.2097-0927.202509067. DOI：

ZHANG Q Z，GUO F Q，CHEN Y Q，et al.DLGAP5 promotes progression of oral squamous cell carcinoma by regulating the Warburg effect［J］.J Army Med Univ，2025，47（22）：2749-2762.DOI：10.16016/j.2097-0927.202509067. DOI：

摘要

目的

探究Discs大同源相关蛋白5（discs large homolog associated protein 5， DLGAP5）在口腔鳞状细胞癌（oral squamous cell carcinoma， OSCC）中的表达水平，并分析其对细胞增殖、迁移、侵袭能力以及Warburg效应的影响。

方法

通过生物信息学分析筛选OSCC潜在治疗靶标。纳入石河子大学第一附属医院2013年1月1日—2024年1月1日72例OSCC组织及40例癌旁组织，收集患者临床病理及预后资料。采用免疫组化检测DLGAP5蛋白表达，并分析其与临床病理特征的关系。生存分析采用Kaplan-Meier法，预后因素分析采用Cox回归模型。通过Western blot和RT-qPCR检测DLGAP5在HOK、SCC-9、SCC-15、SCC-25及CAL-27细胞系中的表达。针对

DLGAP5

基因序列设计4条小干扰RNA（small interfering RNA， siRNA），评估转染效率并选取沉默效果最优的序列作为实验组进行后续功能实验。在CAL-27和SCC-15细胞中沉默DLGAP5表达后，采用Western blot分析己糖激酶2（hexokinase 2， HK2）和烯醇化酶1（enolase 1， ENO1）蛋白表达，通过CCK-8实验、划痕愈合实验、Transwell实验及葡萄糖、乳酸、ATP检测试剂盒分别评估OSCC细胞增殖、迁移、侵袭能力与糖酵解代谢水平。

结果

生物信息学分析显示DLGAP5是OSCC的潜在关键治疗靶点。实验验证显示，DLGAP5在OSCC组织和细胞中均显著高表达（

0.05），患者临床病理及预后资料分析表明，OSCC患者肿瘤TNM分期、淋巴结转移和分化程度与DLGAP5的表达显著相关，且DLGAP5高表达与患者不良预后相关（

0.05）。沉默DLGAP5后，实验组HK2和ENO1的表达显著下降，糖酵解代谢产物水平显著降低（

0.05）；细胞增殖、迁移、侵袭能力显著下降（

0.05）。

结论

DLGAP5在OSCC中高表达，沉默DLGAP5可能间接调控Warburg效应抑制OSCC细胞的增殖、迁移和侵袭，并与患者不良预后相关。

Abstract

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-cance

rous 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 (

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 (

0.05). DLGAP5 silencing resulted in significantly reduced expression of HK2 and ENO1

markedly decreased levels of glycolytic metabolites (

0.05)

and notably declined cell proli

feration

migration

and invasion capabilities (

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.

关键词

Keywords

references

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