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首页> 外文期刊>Biochimica et Biophysica Acta. Gene Regulatory Mechanisms >NF-κB target microRNAs and their target genes in TNFα-stimulated HeLa Cells
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NF-κB target microRNAs and their target genes in TNFα-stimulated HeLa Cells

机译：TNFα刺激的HeLa细胞中的NF-κB靶标microRNA及其靶标基因

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As a transcription factor, NF-κB was demonstrated to regulate the expressions of miRNAs. However, only a few miRNAs have been identified as its targets so far. In this study, by using ChIP-Seq, Genechip and miRNA-Seq techniques, we identified 14 NF-κB target miRNAs in TNFα-stimulated HeLa Cells, including miR-1276, miR-1286, miR-125b-1-3p, miR-219-1-3p, miR-2467-5p, miR-3200-3p, miR-449c-5p, miR-502-5p, miR-548d-5p, miR-30b-3p, miR-3620-5p, miR-340-3p, miR-4454 and miR-4485. Of these miRNAs, 8 detected miRNAs were also NF-κB target misRNAs in TNFα-stimulated HepG2 cells. We also identified 16 target genes of 6 miRNAs including miR-125b-1-3p, miR-1286, miR-502-5p, miR-1276, miR-219-1-3p and miR-30b-3p, in TNFα-stimulated HeLa cells. Target genes of miR-125b-1-3p and miR-1276 were validated in HeLa and HepG2 cells by transfecting their expression plasmids and mimics. Bioinformatic analysis revealed that two potential target genes of miR-1276, BMP2 and CASP9, were enriched in disease phenotypes. The former is enriched in osteoarthritis, and the latter is enriched in Type 2 diabetes and lung cancer, respectively. These findings suggested that this little known miRNA might play roles in these diseases via its two target genes of BMP2 and CASP9. The expression of miR-125b-1 regulated by NF-κB has been reported in diverse cell types under various stimuli, this study found that its expression was also significantly regulated by NF-κB in TNFα-stimulated HeLa and HepG2 cells. Therefore, this miRNA was proposed as a central mediator of NF-κB pathway. These findings provide new insights into the functions of NF-κB in its target miRNA-related biological processes and the mechanisms underlying the regulation of these miRNAs.
机译：作为转录因子，NF-κB被证明可调节miRNA的表达。但是，到目前为止，只有少数miRNA被确定为其靶标。在这项研究中，通过使用ChIP-Seq，Genechip和miRNA-Seq技术，我们在TNFα刺激的HeLa细胞中鉴定了14种NF-κB靶miRNA，包括miR-1276，miR-1286，miR-125b-1-3p，miR -219-1-3p，miR-2467-5p，miR-3200-3p，miR-449c-5p，miR-502-5p，miR-548d-5p，miR-30b-3p，miR-3620-5p，miR -340-3p，miR-4454和miR-4485。在这些miRNA中，检测到的8个miRNA也是TNFα刺激的HepG2细胞中的NF-κB靶misRNA。我们还在TNFα刺激下鉴定了6种miRNA的16个靶基因，包括miR-125b-1-3p，miR-1286，miR-502-5p，miR-1276，miR-219-1-3p和miR-30b-3p。 HeLa细胞。通过转染其表达质粒和模拟物，在HeLa和HepG2细胞中验证了miR-125b-1-3p和miR-1276的靶基因。生物信息学分析表明，miR-1276的两个潜在靶基因BMP2和CASP9富含疾病表型。前者富含骨关节炎，而后者分别富含2型糖尿病和肺癌。这些发现表明，这种鲜为人知的miRNA可能通过其BMP2和CASP9的两个靶基因在这些疾病中起作用。已经报道了在各种刺激下，多种细胞类型中受NF-κB调节的miR-125b-1的表达，该研究发现，在TNFα刺激的HeLa和HepG2细胞中，其表达也受到NF-κB的显着调节。因此，该miRNA被提议作为NF-κB途径的中心介体。这些发现为NF-κB在其与靶标miRNA相关的生物学过程中的功能以及这些miRNA调控的潜在机制提供了新的见解。

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