Eukaryotic initiation factor-2, gamma subunit, suppresses proliferation and regulates the cell cycle via the MAPK/ERK signaling pathway in acute myeloid leukemia
| Autor: | Huo Tan, Bo Li, Xiaozhen Zeng, Yimin Chen, Zhenqian Huang, Jielun Lu, Ling Liu, Yawei Zou, Lihua Xu, Shuyi Chen |
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| Rok vydání: | 2021 |
| Předmět: |
MAPK/ERK pathway
Cancer Research Cell cycle checkpoint Carcinogenesis MAP Kinase Signaling System Eukaryotic Initiation Factor-2 Cell Mice Nude HL-60 Cells Biology Mice Cell Line Tumor medicine Animals Humans RNA Messenger Phosphorylation Cell Proliferation Mice Inbred BALB C Cell Cycle Myeloid leukemia General Medicine Cell cycle medicine.disease Up-Regulation Leukemia Myeloid Acute Leukemia medicine.anatomical_structure Oncology Cell culture Cancer research Heterografts EIF2S3 |
| Zdroj: | Journal of Cancer Research and Clinical Oncology. 147:3157-3168 |
| ISSN: | 1432-1335 0171-5216 |
| DOI: | 10.1007/s00432-021-03712-5 |
| Popis: | 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. 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. 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 |
| Databáze: | OpenAIRE |
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