Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cells
Reticulocalbin‐1 (RCN1) is expressed aberrantly and at a high level in various tumors, including acute myeloid leukemia (AML), yet its impact on AML remains unclear. In this study, we demonstrate that RCN1 knockdown significantly suppresses the viability of bone marrow mononuclear cells (BMMNCs) fro...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-12-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13521 |
| _version_ | 1797401499072987136 |
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| author | Sisi Deng Yuming Pan Na An Fengyi Chen Huan Chen Heng Wang Xiaojing Xu Rui Liu Linlin Yang Xiaomei Wang Xin Du Qiaoxia Zhang |
| author_facet | Sisi Deng Yuming Pan Na An Fengyi Chen Huan Chen Heng Wang Xiaojing Xu Rui Liu Linlin Yang Xiaomei Wang Xin Du Qiaoxia Zhang |
| author_sort | Sisi Deng |
| collection | DOAJ |
| description | Reticulocalbin‐1 (RCN1) is expressed aberrantly and at a high level in various tumors, including acute myeloid leukemia (AML), yet its impact on AML remains unclear. In this study, we demonstrate that RCN1 knockdown significantly suppresses the viability of bone marrow mononuclear cells (BMMNCs) from AML patients but does not affect the viability of granulocyte colony‐stimulating factor (G‐CSF)‐mobilized peripheral blood stem cells (PBSCs) from healthy donors in vitro. Downregulation of RCN1 also reduces the viability of AML cell lines. Further studies showed that the RCN1 knockdown upregulates type I interferon (IFN‐1) expression and promotes AML cell pyroptosis through caspase‐1 and gasdermin D (GSDMD) signaling. Deletion of the mouse Rcn1 gene inhibits the viability of mouse AML cell lines but not the hematopoiesis of mouse bone marrow. In addition, RCN1 downregulation in human AML cells significantly inhibited tumor growth in the NSG mouse xenograft model. Taken together, our results suggest that RCN1 may be a potential target for AML therapy. |
| first_indexed | 2024-03-09T02:11:00Z |
| format | Article |
| id | doaj.art-a576ad614a7041b4acff7e4de527f4bc |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-03-09T02:11:00Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-a576ad614a7041b4acff7e4de527f4bc2023-12-07T11:50:08ZengWileyMolecular Oncology1574-78911878-02612023-12-0117122584260210.1002/1878-0261.13521Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cellsSisi Deng0Yuming Pan1Na An2Fengyi Chen3Huan Chen4Heng Wang5Xiaojing Xu6Rui Liu7Linlin Yang8Xiaomei Wang9Xin Du10Qiaoxia Zhang11Shenzhen Bone Marrow Transplantation Public Service Platform, Shenzhen Institute of Hematology, Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University, Shenzhen University Health Sciences Center ChinaShenzhen Bone Marrow Transplantation Public Service Platform, Shenzhen Institute of Hematology, Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University, Shenzhen University Health Sciences Center ChinaShenzhen Bone Marrow Transplantation Public Service Platform, Shenzhen Institute of Hematology, Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University, Shenzhen University Health Sciences Center ChinaShenzhen Bone Marrow Transplantation Public Service Platform, Shenzhen Institute of Hematology, Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University, Shenzhen University Health Sciences Center ChinaShenzhen Bone Marrow Transplantation Public Service Platform, Shenzhen Institute of Hematology, Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University, Shenzhen University Health Sciences Center ChinaShenzhen Bone Marrow Transplantation Public Service Platform, Shenzhen Institute of Hematology, Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University, Shenzhen University Health Sciences Center ChinaChina National GeneBank, BGI‐Shenzhen ChinaChina National GeneBank, BGI‐Shenzhen ChinaShenzhen Bone Marrow Transplantation Public Service Platform, Shenzhen Institute of Hematology, Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University, Shenzhen University Health Sciences Center ChinaDepartment of Physiology, School of Basic Medical Sciences, International Cancer Center Shenzhen University Health Sciences Center ChinaShenzhen Bone Marrow Transplantation Public Service Platform, Shenzhen Institute of Hematology, Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University, Shenzhen University Health Sciences Center ChinaShenzhen Bone Marrow Transplantation Public Service Platform, Shenzhen Institute of Hematology, Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University, Shenzhen University Health Sciences Center ChinaReticulocalbin‐1 (RCN1) is expressed aberrantly and at a high level in various tumors, including acute myeloid leukemia (AML), yet its impact on AML remains unclear. In this study, we demonstrate that RCN1 knockdown significantly suppresses the viability of bone marrow mononuclear cells (BMMNCs) from AML patients but does not affect the viability of granulocyte colony‐stimulating factor (G‐CSF)‐mobilized peripheral blood stem cells (PBSCs) from healthy donors in vitro. Downregulation of RCN1 also reduces the viability of AML cell lines. Further studies showed that the RCN1 knockdown upregulates type I interferon (IFN‐1) expression and promotes AML cell pyroptosis through caspase‐1 and gasdermin D (GSDMD) signaling. Deletion of the mouse Rcn1 gene inhibits the viability of mouse AML cell lines but not the hematopoiesis of mouse bone marrow. In addition, RCN1 downregulation in human AML cells significantly inhibited tumor growth in the NSG mouse xenograft model. Taken together, our results suggest that RCN1 may be a potential target for AML therapy.https://doi.org/10.1002/1878-0261.13521AMLcaspase‐1GSDMDIFN‐1pyroptosisRCN1 |
| spellingShingle | Sisi Deng Yuming Pan Na An Fengyi Chen Huan Chen Heng Wang Xiaojing Xu Rui Liu Linlin Yang Xiaomei Wang Xin Du Qiaoxia Zhang Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cells Molecular Oncology AML caspase‐1 GSDMD IFN‐1 pyroptosis RCN1 |
| title | Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cells |
| title_full | Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cells |
| title_fullStr | Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cells |
| title_full_unstemmed | Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cells |
| title_short | Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cells |
| title_sort | downregulation of rcn1 promotes pyroptosis in acute myeloid leukemia cells |
| topic | AML caspase‐1 GSDMD IFN‐1 pyroptosis RCN1 |
| url | https://doi.org/10.1002/1878-0261.13521 |
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