Sirt6-Mediated Cell Death Associated with Sirt1 Suppression in Gastric Cancer
Background: Gastric cancer, one of the leading causes of cancer-related death, is strongly associated with <i>H. pylori</i> infection, although other risk factors have been identified. The sirtuin (Sirt) family is involved in the tumorigenesis of gastric cancer, and sirtuins can have pro...
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| Format: | Article |
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MDPI AG
2024-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/2/387 |
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| author | Ji Hyun Seo Somi Ryu So Young Cheon Seong-Jun Lee Seong-Jun Won Chae Dong Yim Hyun-Jin Lee Young-Sool Hah Jung Je Park |
| author_facet | Ji Hyun Seo Somi Ryu So Young Cheon Seong-Jun Lee Seong-Jun Won Chae Dong Yim Hyun-Jin Lee Young-Sool Hah Jung Je Park |
| author_sort | Ji Hyun Seo |
| collection | DOAJ |
| description | Background: Gastric cancer, one of the leading causes of cancer-related death, is strongly associated with <i>H. pylori</i> infection, although other risk factors have been identified. The sirtuin (Sirt) family is involved in the tumorigenesis of gastric cancer, and sirtuins can have pro- or anti-tumorigenic effects. Methods: After determining the overall survival rate of gastric cancer patients with or without Sirt6 expression, the effect of Sirt6 upregulation was also tested using a xenograft mouse model. The regulation of Sirt6 and Sirt1, leading to the induction of mouse double minute 2 homolog (MDM2) and reactive oxygen species (ROS), was mainly analyzed using Western blotting and immunofluorescence staining, and gastric cancer cell (SNU-638) death associated with these proteins was measured using flow cytometric analysis. Results: Sirt6 overexpression led to Sirt1 suppression in gastric cancer cells, resulting in a higher level of gastric cancer cell death in vitro and a reduced tumor volume. ROS and MDM2 expression levels were upregulated by Sirt6 overexpression and/or Sirt1 suppression according to Western blot analysis. The upregulated ROS ultimately led to gastric cancer cell death as determined via Western blot and flow cytometric analysis. Conclusion: We found that the upregulation of Sirt6 suppressed Sirt1, and Sirt6- and Sirt1-induced gastric cancer cell death was mediated by ROS production. These findings highlight the potential of Sirt6 and Sirt1 as therapeutic targets for treating gastric cancer. |
| first_indexed | 2024-03-08T11:02:33Z |
| format | Article |
| id | doaj.art-cc22e2c5061446118aeb0288254e7c16 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-08T11:02:33Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-cc22e2c5061446118aeb0288254e7c162024-01-26T15:37:18ZengMDPI AGCancers2072-66942024-01-0116238710.3390/cancers16020387Sirt6-Mediated Cell Death Associated with Sirt1 Suppression in Gastric CancerJi Hyun Seo0Somi Ryu1So Young Cheon2Seong-Jun Lee3Seong-Jun Won4Chae Dong Yim5Hyun-Jin Lee6Young-Sool Hah7Jung Je Park8Department of Pediatrics, Institute of Health Science, College of Medicine, Gyeongsang National University, Jinju 52725, Republic of KoreaInstitute of Medical Science, Gyeongsang National University, Jinju 52725, Republic of KoreaBiomedical Research Institute, Gyeongsang National University Hospital, Jinju 52727, Republic of KoreaDepartment of Convergence of Medical Sciences, Gyeongsang National University, Jinju 52725, Republic of KoreaInstitute of Medical Science, Gyeongsang National University, Jinju 52725, Republic of KoreaInstitute of Medical Science, Gyeongsang National University, Jinju 52725, Republic of KoreaDepartment of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Chung-Ang University, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong 06973, Republic of KoreaInstitute of Medical Science, Gyeongsang National University, Jinju 52725, Republic of KoreaInstitute of Medical Science, Gyeongsang National University, Jinju 52725, Republic of KoreaBackground: Gastric cancer, one of the leading causes of cancer-related death, is strongly associated with <i>H. pylori</i> infection, although other risk factors have been identified. The sirtuin (Sirt) family is involved in the tumorigenesis of gastric cancer, and sirtuins can have pro- or anti-tumorigenic effects. Methods: After determining the overall survival rate of gastric cancer patients with or without Sirt6 expression, the effect of Sirt6 upregulation was also tested using a xenograft mouse model. The regulation of Sirt6 and Sirt1, leading to the induction of mouse double minute 2 homolog (MDM2) and reactive oxygen species (ROS), was mainly analyzed using Western blotting and immunofluorescence staining, and gastric cancer cell (SNU-638) death associated with these proteins was measured using flow cytometric analysis. Results: Sirt6 overexpression led to Sirt1 suppression in gastric cancer cells, resulting in a higher level of gastric cancer cell death in vitro and a reduced tumor volume. ROS and MDM2 expression levels were upregulated by Sirt6 overexpression and/or Sirt1 suppression according to Western blot analysis. The upregulated ROS ultimately led to gastric cancer cell death as determined via Western blot and flow cytometric analysis. Conclusion: We found that the upregulation of Sirt6 suppressed Sirt1, and Sirt6- and Sirt1-induced gastric cancer cell death was mediated by ROS production. These findings highlight the potential of Sirt6 and Sirt1 as therapeutic targets for treating gastric cancer.https://www.mdpi.com/2072-6694/16/2/387sirtuinsSirtuin1Sirtuin6gastric cancer |
| spellingShingle | Ji Hyun Seo Somi Ryu So Young Cheon Seong-Jun Lee Seong-Jun Won Chae Dong Yim Hyun-Jin Lee Young-Sool Hah Jung Je Park Sirt6-Mediated Cell Death Associated with Sirt1 Suppression in Gastric Cancer Cancers sirtuins Sirtuin1 Sirtuin6 gastric cancer |
| title | Sirt6-Mediated Cell Death Associated with Sirt1 Suppression in Gastric Cancer |
| title_full | Sirt6-Mediated Cell Death Associated with Sirt1 Suppression in Gastric Cancer |
| title_fullStr | Sirt6-Mediated Cell Death Associated with Sirt1 Suppression in Gastric Cancer |
| title_full_unstemmed | Sirt6-Mediated Cell Death Associated with Sirt1 Suppression in Gastric Cancer |
| title_short | Sirt6-Mediated Cell Death Associated with Sirt1 Suppression in Gastric Cancer |
| title_sort | sirt6 mediated cell death associated with sirt1 suppression in gastric cancer |
| topic | sirtuins Sirtuin1 Sirtuin6 gastric cancer |
| url | https://www.mdpi.com/2072-6694/16/2/387 |
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