MicroRNA-106b-5p participates in lead (Pb2+)-induced cell viability inhibition by targeting XIAP in HT-22 and PC12 cells
MicroRNA-106b-5p participates in lead (Pb2+)-induced cell viability inhibition by targeting XIAP in HT-22 and PC12 cells
复制标题
MicroRNA-106b-5p 通过靶向 HT-22 和 PC12 细胞中的 XIAP 参与铅 (Pb2) 诱导的细胞活力抑制
DOI：
10.1016/j.tiv.2020.104876
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发表时间：
2020
影响因子：
3.2
通讯作者：
Zipeng Cao
中科院分区：
文献类型：
--
作者：
Chong Xue;Beipei Kang;Peng Su;Diya Wang;Fang Zhao;Jianbin Zhang;Xiaojing Wang;Haiyang Lang;Zipeng Cao
先前的研究报道了铅（Pb）暴露下X-linked inhibitor of apoptosis protein （XIAP）的表达受到干扰。然而，对XIAP表达的研究主要集中在其转录和翻译后调控上，很少涉及某些不可缺少的microRNAs （miRNAs）调控的转录后机制。有趣的是，我们发现在各种组织中广泛表达的miRNA miR-106b-5p在Pb2+诱导的应激下上调。此外，我们通过生物信息学分析在xiap mRNA的3 ' -UTR中发现了miR-106b-5p的结合位点，并通过荧光素酶报告基因实验提供了miR-106b-5p可以与该调控区域相互作用并发挥作用的证据。我们的研究结果进一步表明，miR-106b-5p下调XIAP蛋白水平，抑制miR-106b-5p逆转了Pb2+处理的HT-22和PC12细胞中XIAP水平和细胞活力的下降。简而言之，我们确定了miR-106b-5p在与Pb神经毒性相关的XIAP表达的转录后调控中的新功能。
Previous studies reported perturbed expressing of X-linked inhibitor of apoptosis protein (XIAP) under lead (Pb) exposure. However, researches on XIAP expression mainly focused on its transcriptional and post-translational regulation, rarely involving post-transcriptional mechanism manipulated by certain indispensable microRNAs (miRNAs). Interestingly, we unveiled that miR-106b-5p, a widely expressed miRNA in various tissues, is upregulated by Pb2+-induced stress. Moreover, we found a binding site for miR-106b-5p in the 3’-UTR of xiap mRNA using bioinformatics analysis, and provided the evidences that miR-106b-5p can interact and function with this regulatory region via luciferase reporter assay. Our results further showed that miR-106b-5p downregulates XIAP protein level, and suppression of miR-106b-5p reverses the decrease in both XIAP level and cell viability in Pb2+-treated HT-22 and PC12 cells. In brief, we identified a novel function of miR-106b-5p in the post-transcriptional regulation of XIAP expression associated with Pb neurotoxicity.