Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cells

被引：1

作者：

Deng, Sisi ^{[1
]}

Pan, Yuming ^{[1
]}

An, Na ^{[1
]}

Chen, Fengyi ^{[1
,2
]}

Chen, Huan ^{[1
]}

Wang, Heng ^{[1
,3
]}

Xu, Xiaojing ^{[4
]}

Liu, Rui ^{[4
]}

Yang, Linlin ^{[1
]}

Wang, Xiaomei ^{[2
]}

Du, Xin ^{[1
]}

Zhang, Qiaoxia ^{[1
]}

机构：

[1] Shenzhen Univ, Hlth Sci Ctr, Shenzhen Peoples Hosp 2, Affiliated Hosp 1,Shenzhen Inst Hematol,Shenzhen B, 3002 Sungang West Rd, Shenzhen 518025, Guangdong, Peoples R China

[2] Shenzhen Univ, Int Canc Ctr, Sch Basic Med Sci, Dept Physiol,Hlth Sci Ctr, Shenzhen, Peoples R China

[3] Shenzhen Longhua Dist Cent Hosp, Dept Hematol, Shenzhen, Peoples R China

[4] BGI Shenzhen, China Natl GeneBank, Shenzhen, Peoples R China

来源：

MOLECULAR ONCOLOGY | 2023年 / 17卷 / 12期

基金：

中国国家自然科学基金;

关键词：

AML; caspase-1; GSDMD; IFN-1; pyroptosis; RCN1; INTERFERON-ALPHA; I INTERFERON; CANCER; IDENTIFICATION; PROLIFERATION; EXPRESSION; TUMOR; BETA; PROTEINS; RETICULOCALBIN-1;

D O I：

10.1002/1878-0261.13521

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：2584 / 2602

页数：19

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