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  • Title: Hsa_circ_0044907 promotes acute myeloid leukemia progression through upregulating oncogene KIT via sequestering miR-186-5p.
    Author: Liu L, Qiang X.
    Journal: Hematology; 2022 Dec; 27(1):960-970. PubMed ID: 36004511.
    Abstract:
    BACKGROUND: It has been reported that circular RNA hsa_circ_0044907 (circ_0044907) expression is overtly elevated in acute myeloid leukemia (AML) patient-derived BMMCs. However, the effect of circ_0044907 on AML progression remains un-clarified. METHODS: Expression of circ_0044907 in BM and AML cells were detected with real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Cell viability, proliferation, apoptosis, and cycle progression were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), 5-ethynyl-2'-deoxyuridine (EDU), and flow cytometry assays. The regulatory mechanism of circ_0044907 was predicted by bioinformatics analysis and validated by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays. In vivo experiments were carried out to verify the function of circ_0044907. RESULTS: Circ_0044907 was overexpressed in AML patient-derived BM and AML cells. Furthermore, circ_0044907 could distinguish AML patients from healthy controls, and high circ_0044907 expression in BM had a poor prognosis for AML patients, implying that circ_0044907 served as a diagnostic and prognostic indicator for AML. Functionally, circ_0044907 silencing reduced cell viability, restrained cell proliferation, arrested cell cycle progression, and induced cell apoptosis in AML cells in vitro. Furthermore, circ_0044907 knockdown decreased AML cell growth in xenograft mouse models. Mechanically, circ_0044907 sponged miR-186-5p to block the inhibiting effect of miR-186-5p on KIT. Silenced miR-186-5p expression weakened circ_0044907 knockdown mediated suppression on AML cell viability, proliferation, and cycle progression. Also, forced KIT expression weakened miR-186-5p upregulation mediated inhibition on AML cell viability, proliferation, and cycle progression. CONCLUSION: Circ_0044907 absorbed miR-186-5p to block the inhibiting impact of miR-186-5p on KIT, thus promoting AML progression.
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