miR-200b在辐射诱导胸腺淋巴瘤中的作用及其机制的初探

摘要/Abstract

摘要： 为了探讨miR-200b在辐射诱导胸腺淋巴瘤中的作用与机制,采用全身分割照射建立BALB/c小鼠辐射诱导胸腺淋巴瘤模型,检测miR-200b表达情况;构建过表达与敲低miR-200b细胞模型,检测该miRNA对细胞增殖、凋亡情况的影响;随后通过miRNA数据库TargetScan分析miRNA潜在靶点,并用双荧光素酶报告系统进行验证,最后采用Spearman方法分析TBK1蛋白与miR-200b表达水平的相关性。结果显示,小鼠辐射诱导胸腺淋巴瘤组织中miR-200b表达下调,过表达miR-200b可明显抑制细胞增殖,增加细胞凋亡,下调miR-200b可促进细胞增殖,减少细胞凋亡;双荧光素酶报告系统提示miR-200b以3' UTR依赖的方式靶向作用于TBK1。在辐射诱导胸腺淋巴瘤样本中,miR-200b表达和TBK1蛋白水平之间存在负相关关系,且TBK1过表达可部分逆转miR-200b介导的细胞生物学效应。结果表明,辐射诱导胸腺淋巴瘤组织中miR-200b表达下调,其直接靶点TBK1表达上调;过表达miR-200b可明显抑制胸腺淋巴瘤细胞增殖,增加细胞凋亡。提示靶向调控miR-200b/TBK1,有望成为防治辐射诱导胸腺淋巴瘤的潜在新途径。

关键词: 辐射致癌, 胸腺淋巴瘤, miR-200b, TBK1, 肿瘤治疗

Abstract: In order to explore the role and mechanism of miR-200b in radiation-induced thymic lymphoma, the radiation-induced thymic lymphoma model of BALB/c mice was established by whole body fractionated irradiation. The expression of miR-200b was detected, and the over expression and knockdown miR-200b cell model was constructed to detect the effect of miRNA on cell proliferation and apoptosis. Then the potential targets of miRNA were analyzed by miRNA database TargetScan and verified by dual luciferase reporter system. Finally, the correlation between TBK1 protein and miR-200b expression was analyzed by Spearman method. The results showed that the expression of miR-200b in mice thymic lymphoma was down-regulated by radiation, over expression of miR-200b could significantly inhibit cell proliferation and promote apoptosis, while down-regulation of miR-200b could promote cell proliferation and inhibit apoptosis, and dual luciferase reporting system suggested that miR-200b targeted TBK1 in a 3'UTR-dependent manner. In radiation-induced thymic lymphoma samples, there was a negative correlation between the expression of miR-200b and the level of TBK1 protein, and the over expression of TBK1 could partially reverse the cellular biological effects mediated by miR-200b. The results showed that the expression of miR-200b was down-regulated and the direct target TBK1 was up-regulated in thymic lymphoma induced by radiation, and the over expression of miR-200b could significantly inhibit the proliferation and increase the apoptosis of thymic lymphoma cells. It is suggested that targeted regulation of miR-200b/TBK1 may be a potential new approach to prevent and treat radiation-induced thymic lymphoma.

Key words: radiation carcinogenesis, radiation induced thymic lymphoma (RITL), miR-200b, TBK1, tumor therapy

中图分类号:

R730

叶晖, 冯珍兰, 程赢, 蔡建明, 蒋建明. miR-200b在辐射诱导胸腺淋巴瘤中的作用及其机制的初探[J]. 辐射防护, 2021, 41(6): 550-557.

YE Hui, FENG Zhelan, CHENG Ying, CAI Jianming, JIANG Jianming. The role of miR-200b in radiation-induced thymic lymphoma and its preliminary mechanism[J]. RADIATION PROTECTION, 2021, 41(6): 550-557.

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