Alteration of the microRNA expression profile in human osteosarcoma cells transfected with APE1 siRNA
Alteration of the microRNA expression profile in human osteosarcoma cells transfected with APE1 siRNA
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转染 APE1 siRNA 的人骨肉瘤细胞中 microRNA 表达谱的改变
DOI：
10.4149/neo_2013_050
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发表时间：
2013-01-01
期刊：
影响因子：
3
通讯作者：
Wang, D.
中科院分区：
文献类型：
--
作者：
Dai, N.;Zhong, Z. Y.;Wang, D.
脱氧核糖核酸内切酶1(APE1)具有DNA修复和氧化还原调节的双重功能，被认为是肿瘤治疗的潜在靶点。用基因芯片和qRT-PCR方法证实miRNA的变化，然后进行基于生物信息学的综合分析。微阵列和qRT-PCR均显示，在APE1基因敲除的HOS细胞中，13个microRNAs(MiRNAs)发生了明显的改变(~gt；2倍)；其中7个(hsa-miR-451、hsa-miR-1290、hsa-miR-765、hsa-miR-483-5p、hsa-miR-513a-5p、hsa-miR-129-5p和hsa-miR-31)表达上调，另外6个(hsa-miR-29b、hsa-miR-197、Has-let-7b、hsa-miR-324-5p、hsa-let-7i和hsa-miR-484)表达下调。此外，通路分析表明，这些受APE1表达影响的miRNAs及其靶基因参与了与发育过程、细胞过程调控、细胞信号转导(如转化生长因子-β、Wnt、MAPK和P53信号转导途径)和癌症相关的通路。在几个下调表达的miRNAs的启动子中都存在与核因子-kappa B、p53、HIF-1α、AP-1、PEBP2、ATF、NF-Y、Pax-2、CREB和c-Myb的可能结合位点，提示APE1可能通过转录因子对miRNAs进行调控。我们的数据表明，由于APE1通过miRNAs调节基因表达的新途径，我们对APE1生物学功能的理解将不可避免地扩大。
Apurinic/apyrimidinic endonuclease1 (APE1), which has the dual functions of DNA repair and redox regulation, is considered to be a promising potential target in cancer treatment. Microarray and qRT-PCR were used to confirm the change of miRNA followed by analysis with comprehensive bioinformatics-based analysis. Both microarray and qRT-PCR demonstrated that 13 microRNAs (miRNAs) were significantly changed (>2-fold) in APE1 knockdown HOS cells; seven of them (hsa-miR-451, hsa-miR-1290, hsa-miR-765, hsa-miR-483-5p, hsa-miR-513a-5p, hsa-miR-129-5p and hsa-miR-31) were up-regulated and the other six (hsa-miR-29b, hsa-miR-197, has-let-7b, hsa-miR-324-5p, hsa-let-7i and hsa-miR-484) were down-regulated. Furthermore, pathway analysis showed that these miRNAs and their target genes affected by the expression of APE1 were involved in pathways relating to developmental processes, regulation of cellular processes, cell signaling (such as TGF-beta, Wnt, MAPK and the p53 signaling pathway) and cancers. There are putative binding sites of NF-kappa B, p53, HIF-1 alpha, AP-1, PEBP2, ATF, NF-Y, Pax-2,CREB and c-Myb in the promoters of several down regulated miRNAs, indicating that APE1 may regulate miRNAs via transcription factors. Our data suggest that our understanding of the biological functions of APE1 will inevitably expand due to the novel pathways that APE1 uses to regulate gene expression through miRNAs.