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...
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2021
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oai:doaj.org-article:b51083088f36478e821450eab2fc34082021-11-14T12:37:36ZCEBPG promotes acute myeloid leukemia progression by enhancing EIF4EBP110.1186/s12935-021-02305-z1475-2867https://doaj.org/article/b51083088f36478e821450eab2fc34082021-11-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02305-zhttps://doaj.org/toc/1475-2867Abstract 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.You JiangShui-Yan WuYan-Ling ChenZi-Mu ZhangYan-Fang TaoYi XieXin-Mei LiaoXiao-Lu LiGen LiDi WuHai-Rong WangRan ZuoHai-Bo CaoJing-Jing PanJuan-Juan YuSi-Qi JiaZheng ZhangXin-Ran ChuYong-Ping ZhangChen-xi FengJian-Wei WangShao-Yan HuZhi-Heng LiJian PanFang FangJun LuBMCarticleCEBPGEIF4EBP1Acute myeloid leukemiaProliferationApoptosisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-12 (2021) |
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CEBPG EIF4EBP1 Acute myeloid leukemia Proliferation Apoptosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 |
| spellingShingle |
CEBPG EIF4EBP1 Acute myeloid leukemia Proliferation Apoptosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 You Jiang Shui-Yan Wu Yan-Ling Chen Zi-Mu Zhang Yan-Fang Tao Yi Xie Xin-Mei Liao Xiao-Lu Li Gen Li Di Wu Hai-Rong Wang Ran Zuo Hai-Bo Cao Jing-Jing Pan Juan-Juan Yu Si-Qi Jia Zheng Zhang Xin-Ran Chu Yong-Ping Zhang Chen-xi Feng Jian-Wei Wang Shao-Yan Hu Zhi-Heng Li Jian Pan Fang Fang Jun Lu CEBPG promotes acute myeloid leukemia progression by enhancing EIF4EBP1 |
| description |
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. |
| format |
article |
| author |
You Jiang Shui-Yan Wu Yan-Ling Chen Zi-Mu Zhang Yan-Fang Tao Yi Xie Xin-Mei Liao Xiao-Lu Li Gen Li Di Wu Hai-Rong Wang Ran Zuo Hai-Bo Cao Jing-Jing Pan Juan-Juan Yu Si-Qi Jia Zheng Zhang Xin-Ran Chu Yong-Ping Zhang Chen-xi Feng Jian-Wei Wang Shao-Yan Hu Zhi-Heng Li Jian Pan Fang Fang Jun Lu |
| author_facet |
You Jiang Shui-Yan Wu Yan-Ling Chen Zi-Mu Zhang Yan-Fang Tao Yi Xie Xin-Mei Liao Xiao-Lu Li Gen Li Di Wu Hai-Rong Wang Ran Zuo Hai-Bo Cao Jing-Jing Pan Juan-Juan Yu Si-Qi Jia Zheng Zhang Xin-Ran Chu Yong-Ping Zhang Chen-xi Feng Jian-Wei Wang Shao-Yan Hu Zhi-Heng Li Jian Pan Fang Fang Jun Lu |
| author_sort |
You Jiang |
| title |
CEBPG promotes acute myeloid leukemia progression by enhancing EIF4EBP1 |
| title_short |
CEBPG promotes acute myeloid leukemia progression by enhancing EIF4EBP1 |
| title_full |
CEBPG promotes acute myeloid leukemia progression by enhancing EIF4EBP1 |
| title_fullStr |
CEBPG promotes acute myeloid leukemia progression by enhancing EIF4EBP1 |
| title_full_unstemmed |
CEBPG promotes acute myeloid leukemia progression by enhancing EIF4EBP1 |
| title_sort |
cebpg promotes acute myeloid leukemia progression by enhancing eif4ebp1 |
| publisher |
BMC |
| publishDate |
2021 |
| url |
https://doaj.org/article/b51083088f36478e821450eab2fc3408 |
| work_keys_str_mv |
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