1. Academic Validation
  2. Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cells

Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cells

  • Mol Oncol. 2023 Sep 25. doi: 10.1002/1878-0261.13521.
Sisi Deng # 1 Yuming Pan # 1 Na An # 1 Fengyi Chen 1 2 Huan Chen 1 Heng Wang 1 3 Xiaojing Xu 4 Rui Liu 4 Linlin Yang 1 Xiaomei Wang 2 Xin Du 1 Qiaoxia Zhang 1
Affiliations

Affiliations

  • 1 Shenzhen 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, Shenzhen, China.
  • 2 International Cancer Center, Department of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen, China.
  • 3 Department of Hematology, Shenzhen Longhua District Central Hospital, Shenzhen, China.
  • 4 China National GeneBank, BGI-, Shenzhen, China.
  • # Contributed equally.
Abstract

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.

Keywords

AML; GSDMD; IFN-1; RCN1; caspase-1; pyroptosis.

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