Analysis of miRNA-mRNA Crosstalk in Radiation-Induced Mouse Thymic Lymphomas to Identify miR-486 as a Critical Regulator by Targeting IGF2BP3 mRNA.

Analysis of miRNA-mRNA Crosstalk in Radiation-Induced Mouse Thymic Lymphomas to Identify miR-486 as a Critical Regulator by Targeting IGF2BP3 mRNA.
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分析辐射诱导的小鼠胸腺淋巴瘤中的 miRNA-mRNA 串扰,以识别 miR-486 作为靶向 IGF2BP3 mRNA 的关键调节因子

DOI:
10.3389/fonc.2020.574001
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发表时间:
2020
影响因子:
4.7
通讯作者:
Liu H
Liu H
中科院分区:
医学3区
文献类型:
--
作者:
Zhao H;Dong S;Du J;Xia P;Liu R;Liu T;Yang Y;Cheng Y;Cai J;Liu C;Gao F;Liu H

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电离辐射是常见的环境致癌物之一。miRNAs在肿瘤的发生、发展、转移过程中起着重要作用。然而,关于miRNA与辐射致癌的关系的研究却鲜有报道。本研究旨在探讨miRNAs在辐射致癌中的作用。本研究建立了放射性胸腺淋巴瘤小鼠模型。利用RTL组织的miRNA阵列,通过预测miRNAs靶基因,建立miRNA-mRNA串扰网络。基于这个网络,我们确定了一个关键的miRNA,miR-486,这是最下调的辐射诱导的致癌作用。然后通过基因敲除小鼠和细胞实验证实miR-486的功能。结果表明,miR-486可通过靶向IGF 2BP 3 mRNA抑制小鼠淋巴瘤细胞的增殖。腺病毒过表达miR-486载体减少体内肿瘤发生。MiR-486基因敲除小鼠具有强烈的辐射诱导的致癌倾向。综上所述,miR-486通过靶向IGF 2BP 3抑制淋巴瘤细胞增殖和辐射诱导的肿瘤发生。
Ionizing radiation is one of the common environmental carcinogens. miRNAs play critical roles in the processes of tumor occurrence, development, metastasis. However, the relationship between radiation-induced carcinogenesis and miRNA rarely reported. This study is aimed to investigate the effect of miRNAs on radiation-induced carcinogenesis. In this study we established the radiation-induced thymic lymphoma mice model. By using miRNA array of RTL tissue and predicting for miRNAs target genes, a miRNA-mRNA crosstalk network was established. Based on this network, we identified a critical miRNA, miR-486, which was the most down-regulated in the radiation-induced carcinogenesis. Then the function of miR-486 was confirmed by using knockout mice and cellular experiments. As a result, miR-486 could inhibit proliferation of mouse lymphoma cells by targeting IGF2BP3 mRNA. The adenovirus over-expression miR-486 vector reduced tumorigenesis in vivo. MiR-486 knockout mice have a strong tendency of radiation-induced carcinogenesis. In conclusion, miR-486 inhibits the proliferation of lymphoma cells and tumorigenesis induced by radiation through targeting IGF2BP3.
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