title: ACER3 supports development of acute myeloid leukemia.
abstract: No new therapy for acute myeloid leukemia (AML) has been approved for more than 30 years. To effectively treat AML, new molecular targets and therapeutic approaches must be identified. In silico analysis of several databases of AML patients demonstrated that the expression of alkaline ceramidase 3 (ACER3) significantly inversely correlates with the overall survival of AML patients. To determine whether ACER3 supports AML development, we employed an shRNA-encoding lentivirus system to inhibit acer3 expression in human AML cells including NB4, U937, and THP-1 cells. The ACER3 deficiency resulted in decreased cell growth and colony formation, elevated apoptosis, and lower AKT signaling of leukemia cells. Our study indicates that ACER3 contributes to AML pathogenesis, and suggests that alkaline ceramidase inhibition is an option to treat AML.
authors.affiliation: Taishan Scholar Immunology Program, Basic Science Institute, Binzhou Medical University, Yantai, Shandong 264003, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Taishan Scholar Immunology Program, Basic Science Institute, Binzhou Medical University, Yantai, Shandong 264003, China.
authors.forename: Yancun
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Taishan Scholar Immunology Program, Basic Science Institute, Binzhou Medical University, Yantai, Shandong 264003, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Li
authors.affiliation: Taishan Scholar Immunology Program, Basic Science Institute, Binzhou Medical University, Yantai, Shandong 264003, China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Taishan Scholar Immunology Program, Basic Science Institute, Binzhou Medical University, Yantai, Shandong 264003, China; Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Taishan Scholar Immunology Program, Basic Science Institute, Binzhou Medical University, Yantai, Shandong 264003, China.
authors.forename: Minjing
authors.initials: M
authors.lastname: Li
authors.affiliation: Taishan Scholar Immunology Program, Basic Science Institute, Binzhou Medical University, Yantai, Shandong 264003, China.
authors.forename: Yuesi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: Alec.Zhang@UTSouthwestern.edu.
authors.forename: Cheng Cheng
authors.initials: CC
authors.lastname: Zhang
mesh_terms: D055574:Alkaline Ceramidase / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D016019:Survival Analysis
chemical_list: D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt; C000619511:ACER3 protein, human; D055574:Alkaline Ceramidase
keywords: Apoptosis; Ceramidase; Leukemia