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Immediate early response 3 gene promotes aggressive progression and autophagy of AML by negatively regulating AKT/mTOR

BACKGROUND: Immediate early response 3 (IER3) plays a vital role in many tumors. This study aims to explore the function and mechanism of IER3 in Acute myeloid leukemia (AML). METHODS: The expression of IER3 in AML was performed by bioinformatics analysis. CCK-8 proliferation assay, flow cytometry c...

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Autores principales: Chen, Yimin, Huang, Zhenqian, Chen, Shuyi, Tan, Li, He, Lang, Yuan, Danyun, Zheng, Lixia, Zhong, Jing hua, Li, Anqiao, Zhang, Heng, Tan, Huo, Xu, Lihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10285281/
https://www.ncbi.nlm.nih.gov/pubmed/37327583
http://dx.doi.org/10.1016/j.tranon.2023.101711
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author Chen, Yimin
Huang, Zhenqian
Chen, Shuyi
Tan, Li
He, Lang
Yuan, Danyun
Zheng, Lixia
Zhong, Jing hua
Li, Anqiao
Zhang, Heng
Tan, Huo
Xu, Lihua
author_facet Chen, Yimin
Huang, Zhenqian
Chen, Shuyi
Tan, Li
He, Lang
Yuan, Danyun
Zheng, Lixia
Zhong, Jing hua
Li, Anqiao
Zhang, Heng
Tan, Huo
Xu, Lihua
author_sort Chen, Yimin
collection PubMed
description BACKGROUND: Immediate early response 3 (IER3) plays a vital role in many tumors. This study aims to explore the function and mechanism of IER3 in Acute myeloid leukemia (AML). METHODS: The expression of IER3 in AML was performed by bioinformatics analysis. CCK-8 proliferation assay, flow cytometry cycle assay, clone formation assay, and tumorigenic ability were used to investigate the effect of IER3 on AML cells. Unbiased label-free quantitative proteomics and label-free quantitative phosphoproteomics analysis were performed. The regulatory relationship between SATB1(Special AT-rich sequence binding protein 1) and IER3 was investigated by Real time-PCR, Western blot, Chromatin immunoprecipitation (CHIP), and PCR. RESULTS: The result indicated that the prognosis of the high IER3 expression group was significantly worse than that of the low expression group. CCK-8 assay showed that IER3 enhanced the proliferation ability. Cell cycle analysis showed IER3 could promote HL60 cells to enter the S phase of DNA synthesis from the quiescent phase. IER3 could stimulate HEL cells to enter mitosis. Clone-formation experiments suggested that IER3 enhanced clonogenic ability.IER3 promoted the tumorigenesis of AML. Further experimental investigation revealed that IER3 promoted autophagy and induced the occurrence and development of AML by negatively regulating the phosphorylation activation of AKT/mTOR pathway. SATB1 was found to bind to the promoter region of IER3 gene and negatively regulate its transcription. CONCLUSION: IER3 could promote the development of AML and induce autophagy of AML cells by negatively regulating the phosphorylation and activation of AKT/mTOR. By the way, SATB1 may negatively target regulates IER3 transcription.
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spelling pubmed-102852812023-06-23 Immediate early response 3 gene promotes aggressive progression and autophagy of AML by negatively regulating AKT/mTOR Chen, Yimin Huang, Zhenqian Chen, Shuyi Tan, Li He, Lang Yuan, Danyun Zheng, Lixia Zhong, Jing hua Li, Anqiao Zhang, Heng Tan, Huo Xu, Lihua Transl Oncol Original Research BACKGROUND: Immediate early response 3 (IER3) plays a vital role in many tumors. This study aims to explore the function and mechanism of IER3 in Acute myeloid leukemia (AML). METHODS: The expression of IER3 in AML was performed by bioinformatics analysis. CCK-8 proliferation assay, flow cytometry cycle assay, clone formation assay, and tumorigenic ability were used to investigate the effect of IER3 on AML cells. Unbiased label-free quantitative proteomics and label-free quantitative phosphoproteomics analysis were performed. The regulatory relationship between SATB1(Special AT-rich sequence binding protein 1) and IER3 was investigated by Real time-PCR, Western blot, Chromatin immunoprecipitation (CHIP), and PCR. RESULTS: The result indicated that the prognosis of the high IER3 expression group was significantly worse than that of the low expression group. CCK-8 assay showed that IER3 enhanced the proliferation ability. Cell cycle analysis showed IER3 could promote HL60 cells to enter the S phase of DNA synthesis from the quiescent phase. IER3 could stimulate HEL cells to enter mitosis. Clone-formation experiments suggested that IER3 enhanced clonogenic ability.IER3 promoted the tumorigenesis of AML. Further experimental investigation revealed that IER3 promoted autophagy and induced the occurrence and development of AML by negatively regulating the phosphorylation activation of AKT/mTOR pathway. SATB1 was found to bind to the promoter region of IER3 gene and negatively regulate its transcription. CONCLUSION: IER3 could promote the development of AML and induce autophagy of AML cells by negatively regulating the phosphorylation and activation of AKT/mTOR. By the way, SATB1 may negatively target regulates IER3 transcription. Neoplasia Press 2023-06-14 /pmc/articles/PMC10285281/ /pubmed/37327583 http://dx.doi.org/10.1016/j.tranon.2023.101711 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Chen, Yimin
Huang, Zhenqian
Chen, Shuyi
Tan, Li
He, Lang
Yuan, Danyun
Zheng, Lixia
Zhong, Jing hua
Li, Anqiao
Zhang, Heng
Tan, Huo
Xu, Lihua
Immediate early response 3 gene promotes aggressive progression and autophagy of AML by negatively regulating AKT/mTOR
title Immediate early response 3 gene promotes aggressive progression and autophagy of AML by negatively regulating AKT/mTOR
title_full Immediate early response 3 gene promotes aggressive progression and autophagy of AML by negatively regulating AKT/mTOR
title_fullStr Immediate early response 3 gene promotes aggressive progression and autophagy of AML by negatively regulating AKT/mTOR
title_full_unstemmed Immediate early response 3 gene promotes aggressive progression and autophagy of AML by negatively regulating AKT/mTOR
title_short Immediate early response 3 gene promotes aggressive progression and autophagy of AML by negatively regulating AKT/mTOR
title_sort immediate early response 3 gene promotes aggressive progression and autophagy of aml by negatively regulating akt/mtor
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10285281/
https://www.ncbi.nlm.nih.gov/pubmed/37327583
http://dx.doi.org/10.1016/j.tranon.2023.101711
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