S100A8-targeting siRNA enhances arsenic trioxide-induced myeloid leukemia cell death by down-regulating autophagy

  • Authors:
    • Liangchun Yang
    • Minghua Yang
    • Hong Zhang
    • Zhuo Wang
    • Yan Yu
    • Min Xie
    • Mingyi Zhao
    • Liying Liu
    • Lizhi Cao
  • View Affiliations

  • Published online on: October 3, 2011     https://doi.org/10.3892/ijmm.2011.806
  • Pages: 65-72
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Abstract

Chemoresistance has become a major obstacle to the successful treatment of leukemia. Autophagy, a regulated process of degradation and recycling of cellular constituents, has recently caught increasing attention for its roles in conferring resistance to various commonly used anticancer therapies. Here we showed that the member of the S100 calcium-binding protein family, S100A8, is a critical regulator of chemoresistance in the autophagy process. It positively correlated with the clinical status in childhood acute myeloblastic leukemia (AML) and it was released from leukemia cells after chemotherapy-induced cytotoxicity. Knockdown of S100A8 expression increased the sensitivity of leukemia cells to chemotherapy and apoptosis. Moreover, suppressing S100A8 expression decreased autophagy as evaluated by the increased expression of the autophagic marker microtubule-associated protein light chain 3 (LC3)-Ⅱ, degradation of SQSTM1/Sequestosome 1 (p62) and formation of autophagosomes. Furthermore, stimuli that enhanced reactive oxygen species (ROS) promoted cytosolic translocation of S100A8 and thereby enhanced autophagy. S100A8 directly interacted with the autophagy protein Beclin1 displacing Bcl-2. These results suggest that S100A8 is a critical pro-autophagic protein that enhances cell survival and regulates chemoresistance in leukemia cells likely through disassociating the Beclin1-Bcl-2 complex.

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January 2012
Volume 29 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Yang L, Yang M, Zhang H, Wang Z, Yu Y, Xie M, Zhao M, Liu L and Cao L: S100A8-targeting siRNA enhances arsenic trioxide-induced myeloid leukemia cell death by down-regulating autophagy. Int J Mol Med 29: 65-72, 2012
APA
Yang, L., Yang, M., Zhang, H., Wang, Z., Yu, Y., Xie, M. ... Cao, L. (2012). S100A8-targeting siRNA enhances arsenic trioxide-induced myeloid leukemia cell death by down-regulating autophagy. International Journal of Molecular Medicine, 29, 65-72. https://doi.org/10.3892/ijmm.2011.806
MLA
Yang, L., Yang, M., Zhang, H., Wang, Z., Yu, Y., Xie, M., Zhao, M., Liu, L., Cao, L."S100A8-targeting siRNA enhances arsenic trioxide-induced myeloid leukemia cell death by down-regulating autophagy". International Journal of Molecular Medicine 29.1 (2012): 65-72.
Chicago
Yang, L., Yang, M., Zhang, H., Wang, Z., Yu, Y., Xie, M., Zhao, M., Liu, L., Cao, L."S100A8-targeting siRNA enhances arsenic trioxide-induced myeloid leukemia cell death by down-regulating autophagy". International Journal of Molecular Medicine 29, no. 1 (2012): 65-72. https://doi.org/10.3892/ijmm.2011.806