实用医学杂志 ›› 2022, Vol. 38 ›› Issue (1): 50-56.doi: 10.3969/j.issn.1006⁃5725.2022.01.010

• 基础研究 • 上一篇    下一篇

EIF4A3结合并稳定基质金属蛋白酶11促进结直肠癌侵袭迁移和上皮间质转化进程

韩思静1,2 贺丹2 李昌平3   

  1. 1 西南医科大学(四川泸州646000);2 成都医学院第二附属医院·核工业四一六医院(成都610000);3 西南 医科大学附属医院(四川泸州646000)

  • 出版日期:2022-01-10 发布日期:2022-01-10
  • 通讯作者: 李昌平 E⁃mail:506854209@qq.com
  • 基金资助:
    四川省医学会青年创新课题(编号:Q19034)

EIF4A3 binds and stabilizes MMP11 to promote invasion,migration and EMT of colorectal cancer

HAN Sijing*,HE Dan,LI Changping.   

  1. Southwest Medical University,Luzhou 646000,China;*The Second Affiliated Hospital of Chengdu Medical College,Nuclear Industry 416 Hospital,Chengdu 610000,China 

  • Online:2022-01-10 Published:2022-01-10
  • Contact: LI Changping E⁃mail:506854209@qq.com

摘要:

目的 探讨 EIF4A3/基质金属蛋白酶(MMP)11 对结直肠癌侵袭、迁移和上皮间质转化 EMT)的影响。方法 从我院获取结直肠癌患者癌及癌旁组织样本各 20 例,生物信息学预测 MMP11 在结直肠癌中的表达水平,qRT⁃PCR western blot 验证结直肠癌组织和细胞中 MMP11 的表达水平。在 结直肠癌细胞中,RIP 实验检测 EIF4A3/MMP11 之间的相互作用,添加放线菌素 D 检测 MMP11 mRNA 的半 衰期。HCT15 细胞中共转染 si⁃EIF4A3 MMP11,Transwell 和划痕实验检测细胞侵袭和迁移能力的变化。 Western blot 检测 EMT 相关蛋白表达的变化。结果 MMP11 在结直肠癌组织和细胞中表达升高(均 P < 0.001),EIF4A3 能和 MMP11 相互作用,并增强 MMP11 mRNA 的稳定性(P < 0.05)。抑制 EIF4A3 表达降低 MMP11 蛋白表达水平并抑制结直肠癌细胞 HCT15 的侵袭、迁移和 EMT 进程(均 P < 0.05),而抑制 EIF4A3 表达同时过表达 MMP11 则能逆转上述作用。结论 MMP11 在结直肠癌组织和细胞中表达升高,EIF4A3 能结合并增强MMP11 mRNA 稳定性,促进结直肠癌侵袭迁移和EMT 进程。

关键词:

EIF4A3, 基质金属蛋白酶11, 结直肠癌, 侵袭迁移, 上皮间质转化

Abstract:

Objective To investigate the effect of EIF4A3 / MMP11 on invasion,migration and EMT of colorectal cancer. Methods A total of 20 samples of cancer and para⁃cancer tissue of patients with colorectal can⁃ cerwere obtained from our hospital. Bioinformatics was used to predict the expression of MMP11 in colorectal cancer. qRT ⁃ PCR and western blot were used to verify the expression of MMP11 in colorectal cancer tissues and cells. In colorectal cancer cells,rip assay was used to detect the interaction between EIF4A3 and MMP11,and actinomycin D was added to detect the half⁃life of MMP11 mRNA. HCT15 cells were co transfected with si⁃EIF4A3 and MMP11. The invasion and migration of HCT15 cells were detected by Transwell and scratch test. The expression of EMT related proteins was detected by western blot. Results The expression of MMP11 was increased in colorectal cancer tissues and cells(all P < 0.001). EIF4A3 interacted with MMP11 and enhanced the stability of MMP11 mRNA (P < 0.05). Inhibition of EIF4A3 expression inhibited the invasion,migration and EMT process of HCT15 cells(all P < 0.05),while inhibition of EIF4A3 expression and overexpression of MMP11 reversed these effects. Conclusion The expression of MMP11 was increased in colorectal cancer tissues and cells. EIF4A3 couldbind and increase the stability of MMP11 mRNA,and promote the invasion,migration and EMT process of colorectal cancer.

Key words:

EIF4A3, MMP11, colorectal cancer, invasive and migration, EMT