Methylation-induced silencing of miR-34a enhances chemoresistance by directly upregulating ATG4B-induced autophagy through AMPK/mTOR pathway in prostate cancer

  • Authors:
    • Haiqiu Liao
    • Yang Xiao
    • Yingbin Hu
    • Yangming Xiao
    • Zhaofa Yin
    • Liang Liu
    • Xiaopeng Kang
    • Yonggang Chen
  • View Affiliations

  • Published online on: October 16, 2015     https://doi.org/10.3892/or.2015.4331
  • Pages: 64-72
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Abstract

miR-34a is downregulated and a regulator of drug resistance in prostate cancer (PCa). However, the mechanism of miR-34a in chemoresistance of PCa remains largely unknown. In the present study, we first confirmed the hypermethylation‑induced downregulation of miR-34a in PCa tissues and cell lines, PC-3 and DU145. Additionally, transfection of miR-34a mimics and demethylation by 5-azacytidine both resulted in the upregulation of miR-34a expression, which further induced declined cell proliferation and the enhanced apoptosis in PCa cells. Upregulation of miR-34a enhanced the chemosensitivity of PC-3 and DU145 cells. Furthermore, overexpression of miR-34a reduced the expression of autophagy-related proteins, ATG4B, Beclin-1 and LC3B II/I in PCa cells and demethylation treatment showed similar effect. ATG4B was confirmed directly by miR-34a targeting in PCa. Finally, downregulated p-AMPK and upregulated p-mTOR were detected in miR-34a overexpressed PCa cells. Collectively, miR-34a enhances chemosensitivity by directly downregulating ATG4B-induced autophagy through AMPK/mTOR pathway in PCa.
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January-2016
Volume 35 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Liao H, Xiao Y, Hu Y, Xiao Y, Yin Z, Liu L, Kang X and Chen Y: Methylation-induced silencing of miR-34a enhances chemoresistance by directly upregulating ATG4B-induced autophagy through AMPK/mTOR pathway in prostate cancer. Oncol Rep 35: 64-72, 2016.
APA
Liao, H., Xiao, Y., Hu, Y., Xiao, Y., Yin, Z., Liu, L. ... Chen, Y. (2016). Methylation-induced silencing of miR-34a enhances chemoresistance by directly upregulating ATG4B-induced autophagy through AMPK/mTOR pathway in prostate cancer. Oncology Reports, 35, 64-72. https://doi.org/10.3892/or.2015.4331
MLA
Liao, H., Xiao, Y., Hu, Y., Xiao, Y., Yin, Z., Liu, L., Kang, X., Chen, Y."Methylation-induced silencing of miR-34a enhances chemoresistance by directly upregulating ATG4B-induced autophagy through AMPK/mTOR pathway in prostate cancer". Oncology Reports 35.1 (2016): 64-72.
Chicago
Liao, H., Xiao, Y., Hu, Y., Xiao, Y., Yin, Z., Liu, L., Kang, X., Chen, Y."Methylation-induced silencing of miR-34a enhances chemoresistance by directly upregulating ATG4B-induced autophagy through AMPK/mTOR pathway in prostate cancer". Oncology Reports 35, no. 1 (2016): 64-72. https://doi.org/10.3892/or.2015.4331