Up-Regulated Expression of miR-23a/b Targeted the Pro-Apoptotic Fas in Radiation-Induced thymic Lymphoma
Up-Regulated Expression of miR-23a/b Targeted the Pro-Apoptotic Fas in Radiation-Induced thymic Lymphoma
复制标题
放射诱导胸腺淋巴瘤中 miR-23a/b 的上调表达靶向促凋亡 Fas
DOI：
10.1159/000356607
复制
发表时间：
2013-01-01
影响因子：
--
通讯作者：
Cai, Jianming
中科院分区：
文献类型：
--
作者：
Li, Bailong;Sun, Mingjuan;Cai, Jianming
背景资料：微小RNA（microRNAs，miRNAs）是一类小的单链非编码RNA，通常与靶mRNA的3 '端非翻译区结合，通过阻断靶mRNA的翻译或降解靶mRNA来诱导转录后基因调控。然而，miR-23在辐射诱导的癌变中的表达水平在很大程度上是未知的。方法：建立放射性诱发的BALB/c小鼠胸腺淋巴瘤模型。通过实时定量PCR检测不同组织和细胞中miR-23 a和miR-23 b miRNA的水平。将miR-23 a/B抑制剂和miR-23 a/B模拟物转染到淋巴瘤细胞中，并通过microRNA靶标预测和荧光素酶测定来鉴定miR-23 a/B的靶标。结果：发现miR-23 a和miR-23 b在辐射诱导的胸腺淋巴瘤组织中表达上调。在淋巴瘤细胞中，miR-23 a/B抑制剂增加细胞死亡和凋亡，而miR-23 a/B模拟物减少细胞死亡和凋亡。计算分析发现miR-23 a/B的靶位点位于Fas mRNA的3' UTR，并通过荧光素酶报告基因分析得到证实。强制过表达miR-23 a/B可降低Fas蛋白水平。此外，Fas的过表达挽救了miR-23的促增殖作用，表明Fas是miR-23功能的直接介导者。此外，与miR-23 a/B上调相反，Fas表达水平在分割辐射诱导的淋巴瘤组织样品中下调，并且与miR-23呈负相关。最后，我们的数据还表明，miR-23 a比miR-23 b更有效地抑制Fas，并且除了保守的种子配对之外的额外区域使miR-23 a的更高调节成为可能。结论：本研究通过建立放射诱导的BALB B/c小鼠胸腺淋巴瘤模型，发现miR-23 a/B b在放射诱导的胸腺淋巴瘤中表达上调，提示miR-23 a/b可能是放射诱导的胸腺淋巴瘤治疗的新靶点。版权所有（C）2013 S. Karger AG，巴塞尔
Background: MicroRNAs (miRNAs) are small, single-stranded, noncoding RNAs, which usually bind to the 3'-untranslated region of target mRNAs and are capable of inducing posttranscriptional gene regulation by blocking translation or by degrading the target mRNA. However, the expression level of miR-23 in radiation induced carcinogenesis is largely unknown. Methods: Radiation induced thymic lymphoma model in BALB/c mice was set up. miR-23a & miR-23b miRNA levels in different tissues and cells were detected by real-time qPCR. miR-23a/b inhibitor and miR-23a/b mimics were transfected to lymphoma cells and the target of miR-23a/b was identified by microRNA target prediction and Luciferase assays. Results: We found that miR-23a & miR-23b were up-regulated in radiation induced thymic lymphoma tissue samples. Cell death and apoptosis were increased by miR-23a/b inhibitor and decreased by miR-23a/b mimics in lymphoma cells. Computational analysis found a putative target site of miR-23a/b in the 3' UTR of Fas mRNA, which was verified by luciferase reporter assay. Forced over-expression of miR-23a/b decreased the level of Fas protein. Moreover, over-expression of Fas rescued the pro-proliferation effect of miR-23, indicating Fas is a direct mediator of miR-23 functions. Furthermore, contrast to miR-23a/b which was up regulated, the Fas expression level was down-regulated and inversely correlated with miR23 in split radiation induced lymphoma tissue samples. Finally, our data also indicates that miR-23a could repress Fas much more potent than miR-23b and the additional region besides conserved seed pairing enables miR-23a's higher regulation. Conclusions: In this study, using a radiation induced thymic lymphoma model in BALB/c mice, We conclude that the expression of miR-23a/b is up-regulated in radiation-induced thymic lymphoma and it maybe a novel therapeutic target of that cancer. Copyright (C) 2013 S. Karger AG, Basel