ACER3 supports development of acute myeloid leukemia

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 (...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2016-09, Vol.478 (1), p.33-38
Main Authors: Chen, Chen, Yin, Yancun, Li, Chunling, Chen, Jinliang, Xie, Jingjing, Lu, Zhigang, Li, Minjing, Wang, Yuesi, Zhang, Cheng Cheng
Format: Article
Language:English
Subjects:
Alkaline Ceramidase - genetics
Alkaline Ceramidase - metabolism
Apoptosis
Cell Line, Tumor
Cell Proliferation
Ceramidase
Gene Expression Regulation, Leukemic
Humans
Leukemia
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - metabolism
Leukemia, Myeloid, Acute - pathology
Proto-Oncogene Proteins c-akt - metabolism
RNA Interference
RNA, Small Interfering - genetics
Signal Transduction
Survival Analysis
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Summary: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. •The expression of ACER3 negatively correlates with the overall survival of AML patients.•ACER3 supports growth of human AML cells by inhibiting apoptosis.•Knockdown of ADCY7 decreases AKT signaling in human AML cells.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2016.07.099