These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Autophagic HuR mRNA degradation induces survivin and MCL1 downregulation in YM155-treated human leukemia cells.
    Author: Chiou JT, Lee YC, Huang CH, Shi YJ, Wang LJ, Chang LS.
    Journal: Toxicol Appl Pharmacol; 2020 Jan 15; 387():114857. PubMed ID: 31837377.
    Abstract:
    The aim of this study was to investigate the mechanism of YM155 cytotoxicity in human chronic myeloid leukemia (CML) cells. YM155-induced apoptosis of human CML K562 cells was characterized by ROS-mediated p38 MAPK activation, mitochondrial depolarization, and survivin and MCL1 downregulation. Moreover, YM155-induced autophagy caused degradation of HuR mRNA and downregulation of HuR protein expression, which resulted in destabilized survivin and MCL1 mRNA. Interestingly, survivin and MCL1 suppression contributed to autophagy-mediated HuR mRNA destabilization in YM155-treated cells. Pretreatment with inhibitors of p38 MAPK or autophagy alleviated YM155-induced autophagy and apoptosis in K562 cells, as well as YM155-induced downregulation of HuR, survivin, and MCL1. Ectopic overexpression of HuR, survivin, or MCL1 attenuated the cytotoxic effect of YM155 on K562 cells. Conversely, YM155 sensitized K562 cells to ABT-199 (a BCL2 inhibitor), and circumvented K562 cell resistance to ABT-199 because of its inhibitory effect on survivin and MCL1 expression. Overall, our data indicate that YM155-induced apoptosis is mediated by inducing autophagic HuR mRNA degradation, and reveal the pathway responsible for YM155-induced downregulation of survivin and MCL1 in K562 cells. Our findings also indicate a similar pathway underlying YM155-induced death in human CML MEG-01 cells.
    [Abstract] [Full Text] [Related] [New Search]