CEBPG promotes acute myeloid leukemia progression by enhancing EIF4EBP1

Abstract

Background Acute myeloid leukemia (AML) is a myeloid neoplasm accounts for 7.6% of hematopoietic malignancies. AML is a complex disease, and understanding its pathophysiology is contributing to the improvement in the treatment and prognosis of AML. In this study, we assessed the expression profile and molecular functions of CCAAT enhancer binding protein gamma (CEBPG), a gene implicated in myeloid differentiation and AML progression. Methods shRNA mediated gene interference was used to down-regulate the expression of CEBPG in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells. Genes and pathways affected by knockdown of CEBPG were identified by gene expression analysis using RNA-seq. One of the genes affected by knockdown of CEBPG was Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1), a known repressor of translation. Knockdown of EIF4EBP1 was used to assess its potential role in AML progression downstream of CEBPG. Results We explored the ChIP-Seq data of AML cell lines and non-AML hematopoietic cells, and found CEBPG was activated through its distal enhancer in AML cell lines. Using the public transcriptomic dataset, the Cancer Cell Line Encyclopedia (CCLE) and western blotting, we also found CEBPG was overexpressed in AML. Moreover, we observed that CEBPG promotes AML cell proliferation by activating EIF4EBP1, thus contributing to the progression of AML. These findings indicate that CEBPG could act as a potential therapeutic target for AML patients. Conclusion In summary, we systematically explored the molecular characteristics of CEBPG in AML and identified CEBPG as a potential therapeutic target for AML patients. Our findings provide novel insights into the pathophysiology of AML and indicate a key role for CEBPG in promoting AML progression.

Molecular subtyping of acute myeloid leukemia through ferroptosis signatures predicts prognosis and deciphers the immune microenvironment

“…The HIF1A module contained 10 nodes and 31 edges, and the ALB module had 11 nodes and 34 edges. Most of the genes in the HIF1A module play leukemia-promoting roles in AML, such as HIF1A ( Abdul-Aziz et al, 2018 ), CEBPG ( Jiang et al, 2021 ), JUN ( Zhou et al, 2017 ), and ATF4 ( Heydt et al, 2018 ). These genes also contributed to treatment resistance in AML ( Zhu et al, 2020 ).…”

C/EBP-Family Redundancy Determines Patient Survival and Lymph Node Involvement in PDAC

“…C/EBPγ is especially well-studied in acute myeloid leukemia (AML), where it promotes cancer progression through the upregulation of EIF4BP1 [ 30 ]. Similarly, in esophageal squamous cell carcinoma (ESCC), C/EBPγ promotes proliferation and migration through the upregulation of the PI3K-Akt signaling pathway and serves as a prognostic marker for poor survival [ 31 ].…”

“…Publicly available datasets were analyzed in this study. This data can be found here: , accession numbers GSE9336 [ 24 ], GSE71729 [ 26 ], GSE36133 [ 27 ], GSE57083, GSE21654 [ 30 ], GSE62165 [ 42 ], GSE21501 [ 43 ], GSE36924 [ 44 ], GSE184585 [ 45 ], GSE36924 [ 45 ], GSE172356 [ 46 ] and , accession numbers E-MEXP-1121 [ 25 ] and E-MTAB-783 [ 28 ] (last accessed on 1 November 2022).…”