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Hsa_circ_0002483 通过调控 miR-758-3p/MYC 轴促进急性髓系白血病进展。

Hsa_circ_0002483 regulates miR-758-3p/MYC axis to promote acute myeloid leukemia progression.

机构信息

Department of Hematology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan, China.

出版信息

Hematol Oncol. 2021 Apr;39(2):243-253. doi: 10.1002/hon.2829. Epub 2020 Dec 21.

DOI:10.1002/hon.2829
PMID:33283885
Abstract

Circular RNAs are relevant to progression of acute myeloid leukemia (AML). Nevertheless, how and whether hsa_circ_0002483 (circ_0002483) participates in AML progression are largely uncertain. The bone marrow samples were harvested from 31 AML patients or 31 normal subjects. Circ_0002483, microRNA (miR)-758-3p and myelocytomatosis oncogene (MYC) abundances were examined via quantitative reverse transcription polymerase chain reaction and Western blot. Cell proliferation, cycle process and apoptosis were analyzed via Cell Counting Kit-8, flow cytometry, caspase 3 activity and related protein levels. Target relationship was investigated by dual-luciferase reporter assay and RNA immunoprecipitation. Circ_0002483 expression was elevated in AML patients and cells. Circ_0002483 silence constrained AML cell proliferation and facilitated cell cycle arrest and apoptosis. miR-758-3p was reduced in AML and decreased via circ_0002483. miR-758-3p down-regulation mitigated the inhibitive influence of circ_0002483 interference on AML progression. MYC was decreased by miR-758-3p, and circ_0002483 could regulate MYC expression by miR-758-3p. miR-758-3p overexpression restrained cell proliferation and promoted cycle arrest and apoptosis via decreasing MYC. Circ_0002483 knockdown repressed AML cell proliferation and promoted cycle arrest and apoptosis via controlling miR-758-3p/MYC axis.

摘要

环状 RNA 与急性髓系白血病 (AML) 的进展有关。然而,hsa_circ_0002483(circ_0002483)是否以及如何参与 AML 进展在很大程度上尚不清楚。从 31 例 AML 患者或 31 例正常对照者中采集骨髓样本。通过定量逆转录聚合酶链反应和 Western blot 检测 circ_0002483、microRNA (miR)-758-3p 和髓细胞瘤癌基因 (MYC) 的丰度。通过细胞计数试剂盒-8、流式细胞术、caspase 3 活性和相关蛋白水平分析细胞增殖、周期进程和凋亡。通过双荧光素酶报告基因检测和 RNA 免疫沉淀研究靶标关系。circ_0002483 在 AML 患者和细胞中表达上调。circ_0002483 沉默抑制 AML 细胞增殖,并促进细胞周期停滞和凋亡。miR-758-3p 在 AML 中减少,并通过 circ_0002483 下调。miR-758-3p 下调减轻了 circ_0002483 干扰对 AML 进展的抑制作用。MYC 被 miR-758-3p 下调,circ_0002483 可以通过 miR-758-3p 调节 MYC 表达。miR-758-3p 过表达通过降低 MYC 来抑制细胞增殖并促进细胞周期停滞和凋亡。circ_0002483 敲低通过控制 miR-758-3p/MYC 轴抑制 AML 细胞增殖并促进细胞周期停滞和凋亡。

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