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SPAG6 silencing induces autophagic cell death in SKM-1 cells via the AMPK/mTOR/ULK1 signaling pathway
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 acut...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291649/ https://www.ncbi.nlm.nih.gov/pubmed/32537026 http://dx.doi.org/10.3892/ol.2020.11607 |
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author | Zhang, Meng Luo, Jie Luo, Xiaohua Liu, Lin |
author_facet | Zhang, Meng Luo, Jie Luo, Xiaohua Liu, Lin |
author_sort | Zhang, Meng |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7291649 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-72916492020-06-12 SPAG6 silencing induces autophagic cell death in SKM-1 cells via the AMPK/mTOR/ULK1 signaling pathway Zhang, Meng Luo, Jie Luo, Xiaohua Liu, Lin Oncol Lett Articles 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. D.A. Spandidos 2020-07 2020-05-13 /pmc/articles/PMC7291649/ /pubmed/32537026 http://dx.doi.org/10.3892/ol.2020.11607 Text en Copyright: © Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Zhang, Meng Luo, Jie Luo, Xiaohua Liu, Lin SPAG6 silencing induces autophagic cell death in SKM-1 cells via the AMPK/mTOR/ULK1 signaling pathway |
title | SPAG6 silencing induces autophagic cell death in SKM-1 cells via the AMPK/mTOR/ULK1 signaling pathway |
title_full | SPAG6 silencing induces autophagic cell death in SKM-1 cells via the AMPK/mTOR/ULK1 signaling pathway |
title_fullStr | SPAG6 silencing induces autophagic cell death in SKM-1 cells via the AMPK/mTOR/ULK1 signaling pathway |
title_full_unstemmed | SPAG6 silencing induces autophagic cell death in SKM-1 cells via the AMPK/mTOR/ULK1 signaling pathway |
title_short | SPAG6 silencing induces autophagic cell death in SKM-1 cells via the AMPK/mTOR/ULK1 signaling pathway |
title_sort | spag6 silencing induces autophagic cell death in skm-1 cells via the ampk/mtor/ulk1 signaling pathway |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291649/ https://www.ncbi.nlm.nih.gov/pubmed/32537026 http://dx.doi.org/10.3892/ol.2020.11607 |
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