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NF-kappa B target microRNAs and their target genes in TNF alpha-stimulated HeLa Cells

文献类型: 外文期刊

作者: Zhou, Fei 1 ; Wang, Wei 1 ; Xing, Yujun 1 ; Wang, Tingting 1 ; Xu, Xinhui 1 ; Wang, Jinke 1 ;

作者机构: 1.Southeast Univ, State Key Lab Bioelect, Nanjing 210096, Jiangsu, Peoples R China

2.Jiangsu Acad Agr Sci, Inst Food Safety & Detect, Nanjing 210014, Jiangsu, Peoples R China

关键词: NF-kappa B;miRNA;Target gene;HeLa cell;TNF alpha

期刊名称:BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS ( 影响因子:4.49; 五年影响因子:5.318 )

ISSN: 1874-9399

年卷期: 2014 年 1839 卷 4 期

页码:

收录情况: SCI

摘要: As a transcription factor, NF-kappa B 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-kappa B target miRNAs in TNF alpha-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-kappa B target misRNAs in TNF alpha-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 TNF alpha-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-kappa B has been reported in diverse cell types under various stimuli, this study found that its expression was also significantly regulated by NF-kappa B in TNF alpha-stimulated HeLa and HepG2 cells. Therefore, this miRNA was proposed as a central mediator of NF-kappa B pathway. These findings provide new insights into the functions of NF-kappa B in its target miRNA-related biological processes and the mechanisms underlying the regulation of these miRNAs. (C) 2014 Elsevier B.V. All rights reserved.

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