ROS-mediated miR-21-5p regulates the proliferation and apoptosis of Cr(VI)-exposed L02 hepatocytes via targeting PDCD4.
ROS-mediated miR-21-5p regulates the proliferation and apoptosis of Cr(VI)-exposed L02 hepatocytes via targeting PDCD4.
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ROS 介导的 miR-21-5p 通过靶向 PDCD4 调节 Cr(VI) 暴露的 L02 肝细胞的增殖和凋亡。
DOI：
10.1016/j.ecoenv.2019.110160
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发表时间：
2020-01
影响因子：
6.8
通讯作者：
Xiao Fang
中科院分区：
文献类型：
--
作者：
Zhang Yujing;Xiao Yuanyuan;Ma Yu;Liang Ningjuan;Liang Yuehui;Lu Chan;Xiao Fang
虽然已经确定了很多关于六价铬[Cr（VI）]诱导的肝毒性的分子机制，更多的仍有待探索。特别是，明确的表观遗传改变的microRNAs（miRNAs），可以负调控mRNA的转录后水平仍然研究不足。本研究采用Annexin V/碘化丙啶（PI）染色法检测细胞凋亡，克隆形成实验和增殖细胞核抗原（PCNA）检测法检测细胞增殖。采用miRNA微阵列技术比较各组间miRNA表达谱的差异。将miR-21- 5 p模拟物（mi）/抑制剂（in）和PDCD 4-siRNA转染到L02肝细胞中。结果表明，Cr（VI）通过活性氧（ROS）诱导L02肝细胞凋亡和抑制增殖，ROS的形成与线粒体损伤，尤其是线粒体呼吸链复合体（MRCC）的抑制密切相关。我们还证实ROS介导的miR-21- 5 p抑制参与了Cr（VI）诱导的细胞凋亡和增殖抑制。此外，程序性细胞死亡蛋白4（PDCD 4），其上调与ROS的过度产生有关，被预测和验证为miR-21- 5 p的靶点。转录因子PDCD 4沉默抑制细胞凋亡并刺激细胞增殖。综上所述，本研究从表观遗传学角度揭示ROS介导的miR-21- 5 p通过靶向PDCD 4调控Cr（VI）暴露L02肝细胞增殖和凋亡，为Cr（VI）暴露人群肝损伤的分子干预和治疗提供了新的靶点。
Although much has been determined about the molecular mechanisms of hexavalent chromium [Cr(VI)]-induced hepatotoxicity, more remains to be explored. In particular, explicit epigenetic alterations of microRNAs (miRNAs) which can negatively regulate mRNAs at post transcriptional level remain understudied. In the present study, cell apoptosis was determined using Annexin V/propidium iodide (PI) staining, while proliferative growth was analyzed by colony formation assay and proliferating cell nuclear antigen (PCNA) detection. miRNA microarray was performed to compare the global miRNAs expression patterns. miR-21-5p mimics (mi)/inhibitor (in), and PDCD4-siRNAs were transfected into L02 hepatocytes. Our results revealed that Cr(VI) induced apoptosis and inhibited proliferation in L02 hepatocytes via reactive oxygen species (ROS), the formation of which is closely related to mitochondrial damage, especially the inhibition of mitochondrial respiratory chain complex (MRCC). We also confirmed that ROS-mediated miR-21-5p inhibition participated in cell apoptosis and proliferative inhibition induced by Cr(VI). Furthermore, programmed cell death protein 4 (PDCD4), the up-regulation of which was related to ROS over-production, was predicted and verified as a target of miR-21-5p. Transcription factor PDCD4 silencing suppressed apoptosis and stimulated cell proliferation. In conclusion, from the perspective of epigenetics, the present study revealed that ROS-mediated miR-21-5p regulated the proliferation and apoptosis of Cr(VI)-exposed L02 hepatocytes via targeting PDCD4, which provided the new targets for molecular intervention and treatment of liver damage in Cr(VI)-exposed population.
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影响因子：
--
作者：
Gaudelot, Kelly;Gibier, Jean-Baptiste;Perrais, Michael
通讯作者：
Perrais, Michael
影响因子：
--
作者：
Pratheeshkumar P;Son YO;Divya SP;Turcios L;Roy RV;Hitron JA;Wang L;Kim D;Dai J;Asha P;Zhang Z;Shi X
通讯作者：
Shi X
DOI：
--
发表时间：
1990
期刊：
IARC monographs on the evaluation of carcinogenic risks to humans
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1002/jat.3358
发表时间：
2017-03
期刊：
Journal of applied toxicology : JAT
影响因子：
--
作者：
Wolenski FS;Shah P;Sano T;Shinozawa T;Bernard H;Gallacher MJ;Wyllie SD;Varrone G;Cicia LA;Carsillo ME;Fisher CD;Ottinger SE;Koenig E;Kirby PJ
通讯作者：
Kirby PJ
影响因子：
3.5
作者：
Beezhold, Kevin;Klei, Linda R.;Barchowsky, Aaron
通讯作者：
Barchowsky, Aaron