[1]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.
 ZHANG Yueting,XIAO Hanxi,SUN Liangbo,et al.Activation of miR1013p/EZH2 pathway enhances sorafenib sensitivity of HepG2 cells[J].J Third Mil Med Univ,2020,42(22):2195-2201.
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
42卷
期数:
2020年第22期
页码:
2195-2201
栏目:
基础医学
出版日期:
2020-11-30

文章信息/Info

Title:
Activation of miR1013p/EZH2 pathway enhances sorafenib sensitivity of HepG2 cells
作者:
张越婷肖翰希孙梁博李涛陈岺曦闫小晶何凤田连继勤
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
Author(s):
ZHANG Yueting XIAO Hanxi SUN Liangbo LI Tao CHEN Lingxi YAN Xiaojing HE Fengtian LIAN Jiqin

Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing, 400038, China

关键词:
microRNA索拉非尼耐药肝癌EZH2
Keywords:
microRNA  sorafenib drug resistance hepatoma enhancer of zeste homolog 2
分类号:
R73;362; R735.7; R979.14
文献标志码:
A
摘要:

目的探讨激活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:
ObjectiveTo investigate the effect of activating the miR1013p/EZH2 pathway on sorafenib sensitivity of HepG2 cells. MethodsHepG2 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. ResultsSorafenib  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). ConclusionActivation of the miR1013p/EZH2 pathway can enhance sorafenib sensitivity of HepG2 cells. 
 

相似文献/References:

[1]秦利燕,王滨,倪振洪,等.索拉非尼诱导肝癌HepG2细胞自噬的机制及意义[J].第三军医大学学报,2013,35(22):2435.
 Qin Liyan,Wang Bin,Ni Zhenhong,et al.Mechanism and significance of sorafenib-induced autophagy in HepG2 cells[J].J Third Mil Med Univ,2013,35(22):2435.
[2]孙梁博,姚洁,李涛,等.二氯乙酸盐激活ROS-JNK通路增强索拉非尼对肝癌细胞增殖的抑制作用[J].第三军医大学学报,2019,41(17):1627.
 SUN Liangbo,YAO Jie,LI Tao,et al.Dichloroacetate enhances sorafenib’s inhibitory effect on proliferation of hepatocellular carcinoma cells by activating ROS-JNK pathway[J].J Third Mil Med Univ,2019,41(22):1627.
[3]肖翰希,张越婷,孙梁博,等.下调miR-4443/TIMP2信号通路增强HepG2细胞对索拉非尼的敏感性[J].第三军医大学学报,2021,43(03):188.
 XIAO Hanxi,ZHANG Yueting,SUN Liangbo,et al.Down-regulation of miR-4443/TIMP2 signaling pathway enhances sorafenib sensitivity in HepG2 cells[J].J Third Mil Med Univ,2021,43(22):188.

更新日期/Last Update: 2020-11-19