The SIRT3 and SIRT6 Promote Prostate Cancer Progression by Inhibiting Necroptosis-Mediated Innate Immune Response
The sirtuins (SIRTs), including seven family members, belong to class III histone deacetylase (HDAC) enzymes, which have been intensively investigated in cancers. Although the function of SIRTs in the cancer immunology is explored, SIRT-specific mechanisms regulating necroptosis-related innate immun...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2020/8820355 |
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| author | Weiwei Fu Hong Li Haiyang Fu Shuchao Zhao Weiping Shi Mengqi Sun Yujun Li |
| author_facet | Weiwei Fu Hong Li Haiyang Fu Shuchao Zhao Weiping Shi Mengqi Sun Yujun Li |
| author_sort | Weiwei Fu |
| collection | DOAJ |
| description | The sirtuins (SIRTs), including seven family members, belong to class III histone deacetylase (HDAC) enzymes, which have been intensively investigated in cancers. Although the function of SIRTs in the cancer immunology is explored, SIRT-specific mechanisms regulating necroptosis-related innate immune response are not clear. In our present study, we found that both the mRNA and protein expression levels of SIRT3 and SIRT6 are significantly increased in the PCa tissues (HR, CI P=3.30E−03; HR, CI P=2.35E−08; and HR, CI P=9.20E−08) and were associated with patients’ Gleason score and nodal metastasis. Furthermore, multivariate analysis showed that the PCa patients with higher expression levels of SIRT3 and SIRT6 had shorter overall survival (OS). Mechanistically, we found that SIRT3 and SIRT6 promote prostate cancer progress by inhibiting RIPK3-mediated necroptosis and innate immune response. Knockdown of both SIRT3 and SIRT6 not only activates TNF-induced necroptosis but also refreshes the corresponding recruitment of macrophages and neutrophils. Overall, our study identified that SIRT3 and SIRT6 are key regulators of necroptosis during prostate cancer progression. |
| format | Article |
| id | doaj-art-bc953d1c23cd42819c96cffe95865403 |
| institution | OA Journals |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-bc953d1c23cd42819c96cffe958654032025-08-20T02:18:51ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/88203558820355The SIRT3 and SIRT6 Promote Prostate Cancer Progression by Inhibiting Necroptosis-Mediated Innate Immune ResponseWeiwei Fu0Hong Li1Haiyang Fu2Shuchao Zhao3Weiping Shi4Mengqi Sun5Yujun Li6Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, ChinaDepartment of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, ChinaDepartment of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, ChinaDepartment of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, ChinaDepartment of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, ChinaDepartment of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, ChinaDepartment of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, ChinaThe sirtuins (SIRTs), including seven family members, belong to class III histone deacetylase (HDAC) enzymes, which have been intensively investigated in cancers. Although the function of SIRTs in the cancer immunology is explored, SIRT-specific mechanisms regulating necroptosis-related innate immune response are not clear. In our present study, we found that both the mRNA and protein expression levels of SIRT3 and SIRT6 are significantly increased in the PCa tissues (HR, CI P=3.30E−03; HR, CI P=2.35E−08; and HR, CI P=9.20E−08) and were associated with patients’ Gleason score and nodal metastasis. Furthermore, multivariate analysis showed that the PCa patients with higher expression levels of SIRT3 and SIRT6 had shorter overall survival (OS). Mechanistically, we found that SIRT3 and SIRT6 promote prostate cancer progress by inhibiting RIPK3-mediated necroptosis and innate immune response. Knockdown of both SIRT3 and SIRT6 not only activates TNF-induced necroptosis but also refreshes the corresponding recruitment of macrophages and neutrophils. Overall, our study identified that SIRT3 and SIRT6 are key regulators of necroptosis during prostate cancer progression.http://dx.doi.org/10.1155/2020/8820355 |
| spellingShingle | Weiwei Fu Hong Li Haiyang Fu Shuchao Zhao Weiping Shi Mengqi Sun Yujun Li The SIRT3 and SIRT6 Promote Prostate Cancer Progression by Inhibiting Necroptosis-Mediated Innate Immune Response Journal of Immunology Research |
| title | The SIRT3 and SIRT6 Promote Prostate Cancer Progression by Inhibiting Necroptosis-Mediated Innate Immune Response |
| title_full | The SIRT3 and SIRT6 Promote Prostate Cancer Progression by Inhibiting Necroptosis-Mediated Innate Immune Response |
| title_fullStr | The SIRT3 and SIRT6 Promote Prostate Cancer Progression by Inhibiting Necroptosis-Mediated Innate Immune Response |
| title_full_unstemmed | The SIRT3 and SIRT6 Promote Prostate Cancer Progression by Inhibiting Necroptosis-Mediated Innate Immune Response |
| title_short | The SIRT3 and SIRT6 Promote Prostate Cancer Progression by Inhibiting Necroptosis-Mediated Innate Immune Response |
| title_sort | sirt3 and sirt6 promote prostate cancer progression by inhibiting necroptosis mediated innate immune response |
| url | http://dx.doi.org/10.1155/2020/8820355 |
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