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Cell Biology and Toxicology

, Volume 34, Issue 6, pp 479–489 | Cite as

miR-146a down-regulation alleviates H2O2-induced cytotoxicity of PC12 cells by regulating MCL1/JAK/STAT pathway

miR-146a down-regulation relieves H2O2-induced PC12 cells cytotoxicity by MCL1/JAK/STAT
  • Xuecheng Yang
  • Xin Mao
  • Xuemei Ding
  • Fengju Guan
  • Yuefeng Jia
  • Lei Luo
  • Bin Li
  • Hailin Tan
  • Caixia CaoEmail author
Original Article
  • 223 Downloads

Abstract

Oxidative stress and miRNAs have been confirmed to play an important role in neurological diseases. The study aimed to explore the underlying effect and mechanisms of miR-146a in H2O2-induced injury of PC12 cells. Here, PC12 cells were stimulated with 200 μM of H2O2 to construct oxidative injury model. Cell injury was evaluated on the basis of the changes in cell viability, migration, invasion, apoptosis, and DNA damage. Results revealed that miR-146a expression was up-regulated in H2O2-induced PC12 cells. Functional analysis showed that down-regulation of miR-146a alleviated H2O2-induced cytotoxicity in PC12 cells. Dual-luciferase reporter and western blot assay verified that MCL1 was a direct target gene of miR-146a. Moreover, anti-miR-146a-mediated suppression on cell cytotoxicity was abated following MCL1 knockdown in H2O2-induced PC12 cells. Furthermore, MCL1 activated JAK/STAT signaling pathway and MCL1 overexpression attenuated H2O2-induced cytotoxicity in PC12 cells by JAK/STAT signaling pathway. In conclusion, this study suggested that suppression of miR-146a abated H2O2-induced cytotoxicity in PC12 cells via regulating MCL1/JAK/STAT pathway.

Keywords

H2O2 JAK/STAT pathway MCL1 miR-146a Oxidative stress PC12 cells 

Abbreviations

AD

Alzheimer’s disease

ATCC

American Tissue Culture Collection

CCK-8

Cell Counting Kit-8

CIS

Chemotherapy-induced senescence

H2O2

Hydrogen peroxide

MCL1

Myeloid cell leukemia 1

MCL1-WT

Wild-type MCL1 report vector

MCL1-MUT

Mutant-type MCL1 report vector

miRNAs

MicroRNAs

ROS

Reactive oxygen species

Notes

Acknowledgements

This study was supported by the Science and Technology Project of Shandong Province (No. 2011YD18006 and No. J16LL58).

Authors’ contributions

This work was designed and conceived by Xuecheng Yang and Caixia Cao. The experiments were carried out by Xuecheng Yang, Bin Li, Lei Luo, and Hailin Tan. Data were interpreted by Xin Mao, Yuefeng Jia, and Xuemei Ding. The manuscript was prepared and reviewed by Xuecheng Yang, Fengju Guan, and Caixia Cao.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to declare.

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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of UrologyThe Affiliated Hospital of Qingdao UniversityQingdaoChina
  2. 2.Department of EndocrinologyThe Affiliated Hospital of Qingdao UniversityQingdaoChina

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