ACSS2介导的上皮间质转化在乙醇促结直肠癌细胞迁移中的作用及机制

孙燕; 王灵巧; 张国伟; 孙凤琼; 王文钰; 徐桂勇; 张爱华; 周紫垣; 杨光红

doi:10.16016/j.2097-0927.202303141

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ACSS2介导的上皮间质转化在乙醇促结直肠癌细胞迁移中的作用及机制

基础医学 | 更新时间：2026-01-09

- ACSS2介导的上皮间质转化在乙醇促结直肠癌细胞迁移中的作用及机制
- Role and mechanism of ACSS2-mediated epithelial-mesenchymal transition in ethanol-promoted migration of colorectal cancer
- 陆军军医大学学报 2023年45卷第17期页码：1806-1818
- 作者机构：
  
  1.550025 贵阳，贵州医科大学公共卫生与健康学院
  2.400038 重庆，陆军军医大学(第三军医大学)军事预防医学系环境卫生学教研室
- 作者简介：
  
  [ 周紫垣，E-mail: ziyuanzhou@tmmu.edu.cn ZHOU Ziyuan, E-mail: ziyuanzhou@tmmu.edu.cn
  [ 杨光红，E-mail: 280446859@qq.com YANG Guanghong, E-mail: 280446859@qq.com
- 基金信息：
  
  国家自然科学基金面上项目(81273156)
- DOI：10.16016/j.2097-0927.202303141
  中图分类号： R730.23;R735.35;R595.6
- 收稿：2023-03-23，
  
  修回：2023-06-08，
  
  纸质出版：2023-09-15
- 稿件说明：
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孙燕, 王灵巧, 张国伟, 等. ACSS2介导的上皮间质转化在乙醇促结直肠癌细胞迁移中的作用及机制[J]. 陆军军医大学学报, 2023,45(17):1806-1818.

Yan SUN, Lingqiao WANG, Guowei ZHANG, et al. Role and mechanism of ACSS2-mediated epithelial-mesenchymal transition in ethanol-promoted migration of colorectal cancer[J]. Journal of Army Medical University, 2023, 45(17): 1806-1818.
孙燕, 王灵巧, 张国伟, 等. ACSS2介导的上皮间质转化在乙醇促结直肠癌细胞迁移中的作用及机制[J]. 陆军军医大学学报, 2023,45(17):1806-1818. DOI： 10.16016/j.2097-0927.202303141.

Yan SUN, Lingqiao WANG, Guowei ZHANG, et al. Role and mechanism of ACSS2-mediated epithelial-mesenchymal transition in ethanol-promoted migration of colorectal cancer[J]. Journal of Army Medical University, 2023, 45(17): 1806-1818. DOI： 10.16016/j.2097-0927.202303141.

摘要

目的

探索

ACSS

acyl-CoA synthetase short chain family member

2)在乙醇促结直肠癌(colorectal cancer，CRC)细胞迁移过程中的作用及其潜在机制。

方法

以在线工具基因表达谱交互式分析(gene expression profiling interactive analysis，GEPIA)和人类蛋白质图谱数据库(the human protein atlas，HPA)分析CRC癌组织和癌旁正常组织中

ACSS

2表达水平；通过ChIP-X富集分析3转录因子数据库(ChIP-X enrichment analysis 3，ChEA3)进行

ACSS

2上游转录因子的富集分析。从癌症基因组图谱(the cancer genome Atlas，TCGA)数据库获得513例CRC患者的

ACSS

2表达水平与相关临床特征参数。以不同浓度乙醇(0、22、44、88 mmol/L)处理HCT116、SW480细胞24、48、72 h，CCK-8实验检测细胞活力；细胞划痕和Transwell实验检测细胞迁移能力；RT-qPCR和Western blot检测相关基因的表达。

结果

① 以22、44、88 mmol/L浓度的乙醇处理48、72 h能显著抑制HCT116和SW480细胞增殖(

＜0.05)。②乙醇处理48 h后，RT-qPCR和Western blot结果显示HCT116、SW480细胞中

ACSS

2的表达明显增加；细胞划痕和Transwell结果显示细胞愈合率和穿孔细胞数均明显增加(

＜0.05)；上皮间质转化(epithelial-mesenchymal transformation，EMT

)相关蛋白E-cadherin表达降低、N-cadherin和Vimentin表达升高(

＜0.05)。③抑制ACSS2表达后，细胞愈合率和穿孔细胞数均较未抑制组降低(

＜0.05)；E-cadherin蛋白表达增加、而N-cadherin和Vimentin蛋白表达降低(

＜0.05)。④HPA数据库分析提示，

ACSS

2在CRC癌组织中的表达明显高于正常组织，其上游调控因子的富集分析提示有8个转录因子可能与ACSS2的表达调控有关，Western blot验证乙醇处理后转录因子CEBPB、SMC1A、CTCF在SW480和HCT116细胞中的表达均显著上调，与ACSS2的表达增加变化一致。⑤513例CRC患者中，

ACSS

2相对高表达组出现外周神经、血管浸润或发生其他远处转移者的比例明显高于相对低表达组(

=6.411，

=0.011)。

结论

乙醇作用后由相关转录因子引起的ACSS2表达增加可能通过诱导EMT促进结直肠癌细胞迁移。

Abstract

Objective

To explore the role and underlying mechanisms of

Acyl-CoA synthetase short chain family member

2 (

ACSS

2) in ethanol-promoted migration of colorectal cancer (CRC) cells.

Methods

The

ACSS

2 expression level in cancer tissues and adjacent normal tissues was analyzed by online tools Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA). The transcription factor enrichment analysis tool ChIP-X Enrichment Analysis 3 (ChEA3) was used to identify

ACSS

2 upstream transcription factors. The

ACSS

2 expression level in cancer tissue and related clinical characteristic parameters of 513 CRC patients were obtained from The Cancer Genome Atlas (TCGA) database. After HCT116 and SW480 cells were treated with ethanol at a dose of 0

44 and 88 mmol/L for 24

48 and 72 h

respectively

cell viability

migration and expression of related molecules at mRNA and protein levels were detected with CCK-8 assay

cell scratch test and transwell assay

and RT-qPCR and Western blotting respectively.

Results

① After treated by ethanol for 48 and 72 h

the 3 doses of 22

44 and 88 mmol/L showed a significant inhibition of proliferation for both HCT116 and SW480 cells (

0.05). ②After 48 h of ethanol treatment

RT-qPCR and Western blotting revealed that the expression levels of

ACSS

2 were increased significantly in HCT116 and SW480 cells

cell scratch test and Transwell assay indicated that the cell healing rate and number of perforated cells were also increased obviously (

0.05)

and epithelial-mesenchymal transformation (EMT) related proteins

E-cadherin was down-regulated

while N-cadherin and Vimentin were up-regulated (all

0.05). ③ Inhibition of

ACSS

2 expression resulted in obviously decreased cell healing rate and number of perforated cells (

0.05)

enhanced expression level of E-cadherin and decrased levels of N-cadherin and Vimentin (all

0.05). ④ HPA database analysis showed that

ACSS

2 has a significantly higher expression level in CRC cancer tissues than in normal tissues

and upstream regulators enrichment analysis suggested 8 transcription factors which probably regulate

ACSS

2 expression. Western blotting showed CEBPB

SMC1A and CTCF had notably increased expression in both SW480 and HCT116 cells after ethanol treatment

which was consistent with the increase trend of

ACSS

2 expression. ⑤ Of the 513 CRC patients

those with higher

ACSS

2 expression had a significantly higher incidence of peripheral nerve or vascular infiltration

and higher rate of existed distant metastases than those with lower expression (

Chi

-square=6.411

=0.011).

Conclusion

Ethanol treatment may probably induce EMT by upregulating

ACSS

2 expression and its upstream transcription factors to promote the migration of CRC cells.

关键词

Keywords

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