Jielun Lu1,2, Shuyi Chen3,2, Huo Tan3, Zhenqian Huang3, Bo Li1, Ling Liu4, Yimin Chen3, Xiaozhen Zeng1, Yawei Zou5, Lihua Xu6,7. 1. Department of Pediatrics, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang West Road, Yuexiu, Guangzhou, 510000, Guangdong, People's Republic of China. 2. Department of Urology and Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Urology, Guangzhou, 510230, Guangdong, People's Republic of China. 3. Department of Hematology, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang West Road, Yuexiu, Guangzhou, 510000, Guangdong, People's Republic of China. 4. Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 51260, People's Republic of China. 5. Department of Pediatrics, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang West Road, Yuexiu, Guangzhou, 510000, Guangdong, People's Republic of China. zouyawei@gzhmu.edu.cn. 6. Department of Hematology, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang West Road, Yuexiu, Guangzhou, 510000, Guangdong, People's Republic of China. xlhua@gzhmu.edu.cn. 7. Department of Urology and Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Urology, Guangzhou, 510230, Guangdong, People's Republic of China. xlhua@gzhmu.edu.cn.
Abstract
PURPOSE: The expression of eukaryotic translation initiation factor-2 subunit 3 (EIF2S3) in patients with non-small cell lung and colorectal cancer is lower than that in healthy individuals. However, the functions of EIF2S3 remain unclear, and its study in leukemia has not been reported. The article aims to explore the role of EIF2S3 in AML (acute myeloid leukemia) and its underlying mechanism. METHODS: Reverse transcription-quantitative PCR was performed to evaluate the expression levels of EIF2S3, and its association with patient prognosis was determined. Inducible HEL-EIF2S3 and HL-60-EIF2S3 cell lines were established by retrovirus infection. Cellular proliferation and the cell cycle were analyzed using Cell Counting Kit-8 and flow cytometric analyses. Tumorigenic ability was evaluated using xenograft nude mouse model. Gene expression profiles were analyzed in HL-60-EIF2S3 cells by next-generation sequencing, and WB analysis was performed to detect the expression of related proteins. RESULTS: The expression of EIF2S3 in patients with AML was lower than that experiencing CR (P = 0.02). Furthermore, EIF2S3 overexpression inhibited cellular proliferation, halted G0/1 to S phase cell cycle progression, and inhibited tumorigenicity (P = 0.015). 479 differentially expressed genes were identified between HL60-EIF2S3 DOX (-) and HL60-EIF2S3 DOX ( +) cells via NGS and several of them involved in MAPK/ERK signaling pathway. The phosphorylation levels of ERK decreased when EIF2S3 was overexpressed (P < 0.050). CONCLUSION: EIF2S3 overexpression may result in a decrease in cellular proliferation, cell cycle arrest, and tumorigenic inhibition via the MAPK/ERK signaling pathway in AML cells.
PURPOSE: The expression of eukaryotic translation initiation factor-2 subunit 3 (EIF2S3) in patients with non-small cell lung and colorectal cancer is lower than that in healthy individuals. However, the functions of EIF2S3 remain unclear, and its study in leukemia has not been reported. The article aims to explore the role of EIF2S3 in AML (acute myeloid leukemia) and its underlying mechanism. METHODS: Reverse transcription-quantitative PCR was performed to evaluate the expression levels of EIF2S3, and its association with patient prognosis was determined. Inducible HEL-EIF2S3 and HL-60-EIF2S3 cell lines were established by retrovirus infection. Cellular proliferation and the cell cycle were analyzed using Cell Counting Kit-8 and flow cytometric analyses. Tumorigenic ability was evaluated using xenograft nude mouse model. Gene expression profiles were analyzed in HL-60-EIF2S3 cells by next-generation sequencing, and WB analysis was performed to detect the expression of related proteins. RESULTS: The expression of EIF2S3 in patients with AML was lower than that experiencing CR (P = 0.02). Furthermore, EIF2S3 overexpression inhibited cellular proliferation, halted G0/1 to S phase cell cycle progression, and inhibited tumorigenicity (P = 0.015). 479 differentially expressed genes were identified between HL60-EIF2S3DOX (-) and HL60-EIF2S3DOX ( +) cells via NGS and several of them involved in MAPK/ERK signaling pathway. The phosphorylation levels of ERK decreased when EIF2S3 was overexpressed (P < 0.050). CONCLUSION:EIF2S3 overexpression may result in a decrease in cellular proliferation, cell cycle arrest, and tumorigenic inhibition via the MAPK/ERK signaling pathway in AML cells.
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