人乙醛脱氢酶家族1成员A3调控胰腺癌细胞的侵袭能力

蔡娇; 李甫; 段江洁; 余时沧

doi:10.16016/j.1000-5404.201904084

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人乙醛脱氢酶家族1成员A3调控胰腺癌细胞的侵袭能力

基础医学 | 更新时间：2026-01-09

- 人乙醛脱氢酶家族1成员A3调控胰腺癌细胞的侵袭能力
- ALDH1A3 regulates invasion ability of pancreatic cancer cells
- 第三军医大学学报 2019年41卷第17期页码：1642-1648
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学) 第一附属医院:全军临床病理学研究所，西南癌症中心
  2.400038 重庆，陆军军医大学(第三军医大学) 第一附属医院:干细胞与再生医学科
  3.400038 重庆，陆军军医大学(第三军医大学) 第一附属医院:肿瘤科
- 作者简介：
  
  [ 余时沧，E-mail:yushicang@163.com YU Shicang, E-mail:yushicang@163.com
- 基金信息：
  
  国家重点研发计划(2016YFA0202104)
- DOI：10.16016/j.1000-5404.201904084
  中图分类号： R345;R730.23;R735.9
- 收稿：2019-04-11，
  
  修回：2019-05-07，
  
  纸质出版：2019-09-15
- 稿件说明：
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蔡娇, 李甫, 段江洁, 等. 人乙醛脱氢酶家族1成员A3调控胰腺癌细胞的侵袭能力[J]. 第三军医大学学报, 2019,41(17):1642-1648.

Jiao CAI, Fu LI, Jiangjie DUAN, et al. ALDH1A3 regulates invasion ability of pancreatic cancer cells[J]. Journal of Third Military Medical University, 2019, 41(17): 1642-1648.
蔡娇, 李甫, 段江洁, 等. 人乙醛脱氢酶家族1成员A3调控胰腺癌细胞的侵袭能力[J]. 第三军医大学学报, 2019,41(17):1642-1648. DOI： 10.16016/j.1000-5404.201904084.

Jiao CAI, Fu LI, Jiangjie DUAN, et al. ALDH1A3 regulates invasion ability of pancreatic cancer cells[J]. Journal of Third Military Medical University, 2019, 41(17): 1642-1648. DOI： 10.16016/j.1000-5404.201904084.

摘要

目的

探讨人乙醛脱氢酶家族1成员A3(aldehyde dehydrogenase 1 family member A3，ALDH1A3)在胰腺癌及正常胰腺组织中的表达情况，并研究其对胰腺癌侵袭的调控及可能的机制。

方法

利用癌症和肿瘤基因图谱(the Cancer Genome Atlas，TCGA)数据库中胰腺癌患者数据集、基因组织表达项目(Genotype-Tissue Expression Project，GTEx)中正常胰腺组织基因表达谱数据和肿瘤细胞系百科全书(Cancer Cell Line Encyclopedia，CCLE)数据库中胰腺癌细胞系的基因表达谱矩阵，分析ALDH家族各亚型的表达情况；Transwell实验检测敲低ALDH1A3对胰腺癌细胞侵袭能力的影响；基因富集分析(gene set enrichment analysis，GSEA)探讨ALDH1A3与JAK/STAT3通路活化的关系。

结果

ALDH1A3在胰腺癌组织中的表达高于正常胰腺组织；在胰腺癌细胞系中的表达高于其他ALDH亚型；下调ALDH1A3可以降低胰腺癌细胞系的侵袭能力；JAK/STAT3通路在ALDH1A3高表达胰腺癌患者中显著富集；下调ALDH1A3可抑制STAT3的磷酸化。

结论

ALDH1A3参与调控胰腺癌细胞的侵袭，其机制可能与JAK/STAT3通路的活化有关。

Abstract

Objective

To detect the expression level of aldehyde dehydrogenase 1 family member A3 (ALDH1A3) in pancreatic cancer and adjacent tissues

and to study its specific mechanism involved in the regulation of invasion of pancreatic cancer cells.

Methods

The ALDH family expression pattern in pancreatic cancer patients and normal pancreatic tissues was analyzed using the gene expression profile matrix of the Cancer Cell Line Encyclopedia (CCLE) database

the Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression Project (GTEx). Transwell assay was used to detect the invasion of pancreatic cancer cells with silencing of ALDH1A3. Gene set enrichment analysis (GSEA) was employed to further explore the relationship between ALDH1A3 and activation of JAK/STAT3 signaling pathway.

Results

The expression level of ALDH1A3 was significantly higher in pancreatic cancer tissues than adjacent normal tissues

and it was of the highest level when compared with the other subtypes in pancreatic cancer cell lines. Down-regulation of ALDH1A3 resulted in the decreased invasion ability of pancreatic cancer cell lines. JAK/STAT3 pathway was significantly enriched in the pancreatic cancer patients with higher expression of ALDH1A3. The silencing of ALDH1A3 induced the decrease of phospho-STAT3.

Conclusion

ALDH1A3 may be involved in the regulation of pancreatic cancer cell invasion through the JAK/STAT3 pathway.

关键词

Keywords

references

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