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SIRT6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the NF-κB pathway
Pancreatic cancer (PC) is a malignant tumor with high mortality worldwide. SIRT6 plays versatile roles in human cancers. However, SIRT6 has rarely been studied in PC. The purpose of the present study was to explore the function and potential mechanism of SIRT6 in PC. The expression of SIRT6 in PC ti...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257961/ https://www.ncbi.nlm.nih.gov/pubmed/35837046 http://dx.doi.org/10.3892/etm.2022.11430 |
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author | Gong, Shuangxi Xiong, Lixin Luo, Zhen Yin, Qinghua Huang, Ming Zhou, Yang Li, Jian |
author_facet | Gong, Shuangxi Xiong, Lixin Luo, Zhen Yin, Qinghua Huang, Ming Zhou, Yang Li, Jian |
author_sort | Gong, Shuangxi |
collection | PubMed |
description | Pancreatic cancer (PC) is a malignant tumor with high mortality worldwide. SIRT6 plays versatile roles in human cancers. However, SIRT6 has rarely been studied in PC. The purpose of the present study was to explore the function and potential mechanism of SIRT6 in PC. The expression of SIRT6 in PC tissues and cells was detected by reverse transcription-quantitative PCR and western blotting. The overall survival time was analyzed through the Kaplan Meier method. Cell viability was measured by the Cell Counting Kit-8 assay. The Fe(2+) content, glucose uptake, lactic acid and ATP production were detected through the corresponding kits. ROS was evaluated using the DCFH-DA detection kit. Protein expression was assessed by immunohistochemistry or western blot analysis. In the present study, SIRT6 was lowly expressed in PC tissues and cells compared with normal tissues and cells. Moreover, the low expression of SIRT6 was associated with a poor prognosis in patients with PC. Upregulation of SIRT6 significantly promoted the ferroptosis and inhibited the glycolysis in PC cells. However, knockdown of SIRT6 resisted ferroptosis and increased glycolysis in PC cells. Further studies found that the activation of NF-κB could reverse the effect of SIRT6 on PC cells. In addition, overexpression of SIRT6 restrained the growth of xenografted tumors and suppressed the nuclear transcription of NF-κB in vivo. Collectively, the present study indicated that SIRT6 promoted ferroptosis and inhibited glycolysis through inactivating the NF-κB signaling pathway in PC. These findings suggested that SIRT6 may become a therapeutic target for PC. |
format | Online Article Text |
id | pubmed-9257961 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-92579612022-07-13 SIRT6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the NF-κB pathway Gong, Shuangxi Xiong, Lixin Luo, Zhen Yin, Qinghua Huang, Ming Zhou, Yang Li, Jian Exp Ther Med Articles Pancreatic cancer (PC) is a malignant tumor with high mortality worldwide. SIRT6 plays versatile roles in human cancers. However, SIRT6 has rarely been studied in PC. The purpose of the present study was to explore the function and potential mechanism of SIRT6 in PC. The expression of SIRT6 in PC tissues and cells was detected by reverse transcription-quantitative PCR and western blotting. The overall survival time was analyzed through the Kaplan Meier method. Cell viability was measured by the Cell Counting Kit-8 assay. The Fe(2+) content, glucose uptake, lactic acid and ATP production were detected through the corresponding kits. ROS was evaluated using the DCFH-DA detection kit. Protein expression was assessed by immunohistochemistry or western blot analysis. In the present study, SIRT6 was lowly expressed in PC tissues and cells compared with normal tissues and cells. Moreover, the low expression of SIRT6 was associated with a poor prognosis in patients with PC. Upregulation of SIRT6 significantly promoted the ferroptosis and inhibited the glycolysis in PC cells. However, knockdown of SIRT6 resisted ferroptosis and increased glycolysis in PC cells. Further studies found that the activation of NF-κB could reverse the effect of SIRT6 on PC cells. In addition, overexpression of SIRT6 restrained the growth of xenografted tumors and suppressed the nuclear transcription of NF-κB in vivo. Collectively, the present study indicated that SIRT6 promoted ferroptosis and inhibited glycolysis through inactivating the NF-κB signaling pathway in PC. These findings suggested that SIRT6 may become a therapeutic target for PC. D.A. Spandidos 2022-06-08 /pmc/articles/PMC9257961/ /pubmed/35837046 http://dx.doi.org/10.3892/etm.2022.11430 Text en Copyright: © Gong et al. https://creativecommons.org/licenses/by-nc-nd/4.0/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 Gong, Shuangxi Xiong, Lixin Luo, Zhen Yin, Qinghua Huang, Ming Zhou, Yang Li, Jian SIRT6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the NF-κB pathway |
title | SIRT6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the NF-κB pathway |
title_full | SIRT6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the NF-κB pathway |
title_fullStr | SIRT6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the NF-κB pathway |
title_full_unstemmed | SIRT6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the NF-κB pathway |
title_short | SIRT6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the NF-κB pathway |
title_sort | sirt6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the nf-κb pathway |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257961/ https://www.ncbi.nlm.nih.gov/pubmed/35837046 http://dx.doi.org/10.3892/etm.2022.11430 |
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