CEBPG promotes acute myeloid leukemia progression by enhancing EIF4EBP1

Cancer Cell International

Yan-Fang Tao¹  Shui-Yan Wu¹  Jun Lu¹  You Jiang¹  Jian Pan¹  Jing-Jing Pan¹  Xin-Ran Chu¹  Yong-Ping Zhang¹  Shao-Yan Hu¹  Juan-Juan Yu²  Si-Qi Jia²  Zheng Zhang²  Gen Li²  Jian-Wei Wang²  Zi-Mu Zhang²  Xin-Mei Liao²  Ran Zuo²  Yi Xie²  Di Wu²  Yan-Ling Chen²  Xiao-Lu Li²  Fang Fang²  Hai-Rong Wang²  Zhi-Heng Li²  Hai-Bo Cao²  Chen-xi Feng² 

[1] Department of Hematology, Children’s Hospital of Soochow University;Institute of Pediatric Research, Children’s Hospital of Soochow University;

关键词: CEBPG;    EIF4EBP1;    Acute myeloid leukemia;    Proliferation;    Apoptosis;   

DOI  :  10.1186/s12935-021-02305-z

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown