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Prognosis and regulation of an adenylyl cyclase network in acute myeloid leukemia
- Source :
- Aging (Albany NY)
- Publication Year :
- 2020
- Publisher :
- Impact Journals, LLC, 2020.
-
Abstract
- We explored the roles of adenylyl cyclases (ADCYs) in acute myeloid leukemia (AML). Expression ADCYs in AML and their effect on prognosis was analyzed using data from Oncomine, GEPIA and cBioPortal databases. Frequently altered neighbor genes (FANGs) of ADCYs were detected using the 3D Genome Browser, after which the functions of these FANGs were predicted using Metascape tools. Cell viability and apoptosis were assessed using CCK-8 and Annexin V-FITC/PI kits. Expression levels of ADCYs were higher in AML cells lines and in bone marrow-derived mononuclear cells from AML patients than in control cells, and were predictive of a poor prognosis. A total of 58 ADCY FANGs were identified from the topologically associating domains on the basis of the Hi-C data. Functional analysis of these FANGs revealed abnormal activation of the MAPK signaling pathway. Drug sensitivity tests showed that fasudil plus trametinib or sapanisertib had a synergistic effect suppressing AML cell viability and increasing apoptosis. These findings suggest that dysregulation of ADCY expression leads to altered signaling in the MAPK pathway in AML and that the ADCY expression profile may be predictive of prognosis in AML patients.
- Subjects :
- MAPK/ERK pathway
Aging
Cell Survival
MAP Kinase Signaling System
Datasets as Topic
Apoptosis
Kaplan-Meier Estimate
Biology
Adenylyl cyclase
ADCYs factors
chemistry.chemical_compound
AML
Annexin
Cell Line, Tumor
hemic and lymphatic diseases
Antineoplastic Combined Chemotherapy Protocols
Biomarkers, Tumor
Humans
prognostic value
Gene Regulatory Networks
Protein Interaction Maps
Viability assay
Protein Kinase Inhibitors
Sapanisertib
Trametinib
Gene Expression Regulation, Leukemic
Gene Expression Profiling
Computational Biology
Myeloid leukemia
Drug Synergism
Cell Biology
Prognosis
3D genome
Leukemia, Myeloid, Acute
chemistry
Mutation
MAPK signaling pathway
Cancer research
Drug Screening Assays, Antitumor
Research Paper
Adenylyl Cyclases
Subjects
Details
- ISSN :
- 19454589
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Aging
- Accession number :
- edsair.doi.dedup.....73b44d3edc8df9ab0900478bddc8e46e