title: IRF3 is involved in human acute myeloid leukemia through regulating the expression of miR-155.
abstract: Acute myeloid leukemia (AML) is a serious disease of the hematopoietic system characterized by de-differentiation and uncontrolled proliferation of immature hematopoietic precursor cells in the bone marrow. However, the underlying mechanism of AML development remains largely unknown. Here in this study, we report the function of IRF3, a member of the interferon-regulatory factor (IRF) family, in human AML. We first show that IRF3 mRNA and protein levels are significantly up-regulated in human AML compared with healthy donors. IRF3 knockdown inhibits cellular proliferation and colony formation in OCI/AML-2 and OCI/AML-3 cells. In addition, IRF3 knockdown induces apoptosis of OCI/AML-2 and OCI/AML-3 cells, whereas IRF3 overexpression promotes cell survival. Further mechanism study shows that IRF3 is positively correlated with miR-155, which is considered as an oncogenic microRNA in AML. We show that IRF3 binds to the promoter of miR-155 and promotes the expression of miR-155 in OCI/AML-2 and OCI/AML-3 cells. In conclusion, our evidence show that IRF3 overexpression in AML promotes cell growth and survival, and miR-155 is involved, indicating that IRF3 may be a potential new biomarker and therapeutic target for AML.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450052, China.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Tian
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450052, China.
authors.forename: Zhong-Xing
authors.initials: ZX
authors.lastname: Jiang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450052, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450052, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450052, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Tang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450052, China.
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Huang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450052, China. Electronic address: lingsun1@21cn.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Sun
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation / Q000235:genetics
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C524942:MIRN155 microRNA, human; D035683:MicroRNAs
keywords: Acute myeloid leukemia; IRF3; miR-155