Research Paper Volume 12, Issue 12 pp 11864—11877
Prognosis and regulation of an adenylyl cyclase network in acute myeloid leukemia
- 1 Department of Hematologic Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
- 2 State Key Laboratory of Oncology in South China, Guangzhou, China
- 3 Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- 4 National Research Center for Translational Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Received: November 4, 2019 Accepted: May 20, 2020 Published: June 22, 2020https://doi.org/10.18632/aging.103357
How to Cite
Copyright © 2020 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
AML: Acute Myeloid Leukemia; ADCYs: Adenylyl Cyclases; FANGs: Frequently Altered Neighbor Genes; TADs: Topologically Associating Domains; CRC: Colorectal Cancer; HCC: Hepatocellular Carcinoma; TCGA: The Cancer Genome Atlas; GTEx: Genotype-Tissue Expression; GEPIA: Gene Expression Profiling Interactive Analysis; OS: Overall Survival; DEGS: Differentially Expressed Genes; KEGG: Kyoto Encyclopedia of Genes and Genomes.