hsa_circ_0044907 通过海绵吸附 miR-186-5p 而上调癌基因 KIT 促进急性髓系白血病进展。
Hsa_circ_0044907 promotes acute myeloid leukemia progression through upregulating oncogene KIT via sequestering miR-186-5p.
机构信息
Department of Laboratory, Liangjiang New Area First People's Hospital, Chongqing, People's Republic of China.
Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, People's Republic of China.
出版信息
Hematology. 2022 Dec;27(1):960-970. doi: 10.1080/16078454.2022.2113574.
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. 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 . 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.
背景
据报道，环状 RNA hsa_circ_0044907（circ_0044907）在急性髓系白血病（AML）患者来源的 BMMCs 中明显上调。然而，circ_0044907 对 AML 进展的影响仍不清楚。
方法
采用实时定量逆转录聚合酶链反应（RT-qPCR）检测 BM 和 AML 细胞中 circ_0044907 的表达。采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）、5-乙炔基-2'-脱氧尿苷（EDU）和流式细胞术检测细胞活力、增殖、凋亡和细胞周期进程。通过生物信息学分析预测 circ_0044907 的调控机制，并通过双荧光素酶报告、RNA 下拉和 RNA 免疫沉淀（RIP）实验进行验证。进行实验以验证 circ_0044907 的功能。
结果
circ_0044907 在 AML 患者来源的 BM 和 AML 细胞中高表达。此外，circ_0044907 可区分 AML 患者和健康对照者，BM 中高 circ_0044907 表达对 AML 患者预后不良，表明 circ_0044907 可作为 AML 的诊断和预后指标。功能上，circ_0044907 沉默降低了 AML 细胞活力，抑制了细胞增殖，阻滞了细胞周期进程，并诱导了 AML 细胞凋亡。此外，circ_0044907 敲低抑制了异种移植小鼠模型中 AML 细胞的生长。机制上，circ_0044907 海绵吸附 miR-186-5p 以阻断 miR-186-5p 对 KIT 的抑制作用。沉默 miR-186-5p 表达减弱了 circ_0044907 敲低对 AML 细胞活力、增殖和细胞周期进程的抑制作用。此外，强制表达 KIT 减弱了 miR-186-5p 上调对 AML 细胞活力、增殖和细胞周期进程的抑制作用。
结论
circ_0044907 吸收 miR-186-5p 以阻断 miR-186-5p 对 KIT 的抑制作用，从而促进 AML 进展。
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