Open Access

SPAG6 silencing induces autophagic cell death in SKM‑1 cells via the AMPK/mTOR/ULK1 signaling pathway

  • Authors:
    • Meng Zhang
    • Jie Luo
    • Xiaohua Luo
    • Lin Liu
  • View Affiliations

  • Published online on: May 13, 2020     https://doi.org/10.3892/ol.2020.11607
  • Pages: 551-560
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

As a member of the cancer‑testis antigen family, sperm‑associated antigen 6 (SPAG6) has been reported to be associated with the pathogenesis of myelodysplastic syndromes (MDS). Previous studies have demonstrated that SPAG6 is upregulated in bone marrow from patients with MDS and MDS‑transformed acute myeloid leukemia and that knockdown of SPAG6 expression levels suppressed proliferation and promote apoptosis and differentiation in SKM‑1 cells. However, the association between SPAG6 and autophagy in SKM‑1 cells remains unclear. Hence, the aim of the present study was to investigate this association and its underlying mechanism. The present study used a short hairpin RNA (shRNA) lentivirus to silence SPAG6 expression levels in SKM‑1 cells and demonstrated that SPAG6 knockdown increased autophagy and apoptosis. Furthermore, pharmacologically inhibiting autophagy with chloroquine and 3‑methyladenine decreased SPAG6 knockdown‑mediated apoptosis, indicating that SPAG6 knockdown‑mediated autophagy promoted apoptosis in SKM‑1 cells. Additionally, compared with the expression levels in negative control‑shRNA lentivirus‑transfected SKM‑1 cells, the protein expression levels of phosphorylated AMP‑activated protein kinase (p‑AMPK) and phosphorylated unc‑51‑like autophagy activating kinase 1 (p‑ULK1) were upregulated, while phosphorylated mammalian target of rapamycin (p‑mTOR) protein expression was downregulated in SPAG6‑shRNA lentivirus‑transfected cells. Moreover, inhibiting AMPK expression levels with Compound C, a specific inhibitor of AMPK, attenuated SPAG6 knockdown‑induced autophagy and apoptosis, suggesting that AMPK‑mediated autophagy enhanced the pro‑apoptotic effect of SPAG6 knockdown in SKM‑1 cells. Taken together, the results of the present study demonstrated that SPAG6 silencing triggered autophagy via regulation of the AMPK/mTOR/ULK1 signaling pathway, which further contributed to the apoptosis of SKM‑1 cells induced by SPAG6 knockdown. Thus, the current results indicate that SPAG6 may be a potential therapeutic target against MDS, and that autophagy may represent a potential mechanism for the treatment of MDS.

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July 2020
Volume 20 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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APA
Zhang, M., Luo, J., Luo, X., & Liu, L. (2020). SPAG6 silencing induces autophagic cell death in SKM‑1 cells via the AMPK/mTOR/ULK1 signaling pathway. Oncology Letters, 20, 551-560. https://doi.org/10.3892/ol.2020.11607
MLA
Zhang, M., Luo, J., Luo, X., Liu, L."SPAG6 silencing induces autophagic cell death in SKM‑1 cells via the AMPK/mTOR/ULK1 signaling pathway". Oncology Letters 20.1 (2020): 551-560.
Chicago
Zhang, M., Luo, J., Luo, X., Liu, L."SPAG6 silencing induces autophagic cell death in SKM‑1 cells via the AMPK/mTOR/ULK1 signaling pathway". Oncology Letters 20, no. 1 (2020): 551-560. https://doi.org/10.3892/ol.2020.11607