激活miR-101-3p/EZH2通路增敏索拉非尼抗肝癌HepG2细胞的效果

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激活miR-101-3p/EZH2通路增敏索拉非尼抗肝癌HepG2细胞的效果

基础医学 | 更新时间：2026-01-09

- 激活miR-101-3p/EZH2通路增敏索拉非尼抗肝癌HepG2细胞的效果
- Activation of miR-101-3p/EZH2 pathway enhances sorafenib sensitivity of HepG2 cells
- 第三军医大学学报 2020年42卷第22期页码：2195-2201
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)基础医学院生物化学与分子生物学教研室
- 作者简介：
  
  [ 连继勤，E-mail:lianjiqin@sina.com LIAN Jiqin, E-mail:lianjiqin@sina.com
- 基金信息：
  
  国家自然科学基金面上项目(81572375);重庆市自然科学基金面上项目(CSTC2018jcyjA2018)
- DOI：10.16016/j.1000-5404.202007062
  中图分类号： R73-362;R735.7;R979.14
- 收稿：2020-07-08，
  
  修回：2020-09-18，
  
  纸质出版：2020-11-30
- 稿件说明：
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张越婷, 肖翰希, 孙梁博, 等. 激活miR-101-3p/EZH2通路增敏索拉非尼抗肝癌HepG2细胞的效果[J]. 第三军医大学学报, 2020,42(22):2195-2201.

Yueting ZHANG, Hanxi XIAO, Liangbo SUN, et al. Activation of miR-101-3p/EZH2 pathway enhances sorafenib sensitivity of HepG2 cells[J]. Journal of Third Military Medical University, 2020, 42(22): 2195-2201.
张越婷, 肖翰希, 孙梁博, 等. 激活miR-101-3p/EZH2通路增敏索拉非尼抗肝癌HepG2细胞的效果[J]. 第三军医大学学报, 2020,42(22):2195-2201. DOI： 10.16016/j.1000-5404.202007062.

Yueting ZHANG, Hanxi XIAO, Liangbo SUN, et al. Activation of miR-101-3p/EZH2 pathway enhances sorafenib sensitivity of HepG2 cells[J]. Journal of Third Military Medical University, 2020, 42(22): 2195-2201. DOI： 10.16016/j.1000-5404.202007062.

摘要

目的

2

探讨激活miR-101-3p/EZH2通路在增敏索拉非尼抗肝癌HepG2细胞中的意义。

方法

2

将人肝癌细胞HepG2分成对照组(DMSO)和索拉非尼处理组(10 μmol/L)，处理24 h后，定量PCR检测miR-101-3p表达水平变化；生物信息学预测miR-101-3p结合的靶基因；在肝癌细胞中过表达miR-101-3p后Western blot和定量PCR检测zeste同源蛋白2增强子(enhancer of zeste homolog 2 protein，EZH2)表达水平变化；双荧光素酶报告基因实验验证miR-101-3p和EZH2的靶向关系；Western blot检测索拉非尼处理对EZH2表达水平的影响；在HepG2细胞中过表达miR-101-3p或添加EZH2抑制剂EPZ-6438后联合索拉非尼处理，CCK-8检测对HepG2细胞存活的影响。

结果

2

索拉非尼处理后HepG2细胞中miR-101-3p表达水平显著降低(

P

<

0.05)；miR-101-3p可在HepG2细胞中下调EZH2的表达(

P

<

0.05)；miR-101-3p与EZH2 mRNA 3’-UTR存在直接结合(

P

<

0.05)；索拉非尼处理后HepG2细胞中EZH2表达水平显著升高(

P

<

0.05)；过表达miR-101-3p或EZH2抑制剂EPZ-6438均可增加索拉非尼对HepG2细胞杀伤的敏感性(

P

<

0.05)。

结论

2

激活miR-101-3p/EZH2通路可增敏索拉非尼的抗肝癌细胞HepG2效果。

Abstract

Objective

2

To investigate the effect of activating the miR-101-3p/EZH2 pathway on sorafenib sensitivity of HepG2 cells.

Methods

2

HepG2 cells treated with sorafenib (10 μmol/L) for 24 h were examined for protein expression of enhancer of zeste homolog 2 (EZH2) using Western blotting and for mRNA expression of EZH2 and miR-101-3p using RT-qPCR. The interaction between miR-101-3p and EZH2 mRNA was analyzed through informatics analysis and verified using dual luciferase reporter assay. HepG2 cells were transfected with miR-101-3p mimic or treated with the EZH2 inhibitor EPZ-6438 followed by treatment with sorafenib for 24 h

and the change in cell proliferation was assessed using CCK-8 assay.

Results

2

Sorafenib obviously decreased the expression of miR-101-3p in HepG2 cells (

P

<

0.05). Informatics analysis showed that miR-101-3p could bind to the 3'-UTR of EZH2 mRNA

and transfection with miR-101-3p significantly inhibited the expression of EZH2 in HepG2 cells (

P

<

0.05). Sorafenib treatment significantly increased the expression of EZH2 in HepG2 cells (

P

<

0.05). Both miR-101-3p over-expression and EPZ-6438 treatment resulted in significantly increased sorafenib sensitivity of HepG2 cells (

P

<

0.05).

Conclusion

2

Activation of the miR-101-3p/EZH2 pathway can enhance sorafenib sensitivity of HepG2 cells.

关键词

Keywords

references

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