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Research Paper|Volume 12, Issue 12|pp 11864—11877

Prognosis and regulation of an adenylyl cyclase network in acute myeloid leukemia

Si-Liang Chen1,2,3, Fang Hu1,2,3, Da-Wei Wang4, Zhe-Yuan Qin1,2,3, Yang Liang1,2,3, Yu-Jun Dai1,2,3
  • 1Department of Hematologic Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
  • 2State Key Laboratory of Oncology in South China, Guangzhou, China
  • 3Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
  • 4National Research Center for Translational Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
* Equal contribution
Received: November 4, 2019Accepted: May 20, 2020Published: June 22, 2020
https://doi.org/10.18632/aging.103357

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.

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.