抑制lrp16基因表达药物的生物信息学筛查

Bioinformatics Scan of Factors with Inhibitory Effect on lrp16 Gene Expression

本研究通过分析lrp16基因启动子的DNA序列,在负性调控功能区内寻找顺式元件,为筛选有抑制lrp16基因表达的药物奠定基础。以人类基因组数据库和计算机互联网为平台,钓取lrp16基因5′侧翼区3000bp非编码DNA序列和mRNA序列中的ORF序列;利用TESS和Genomax等在线启动子分析软件在人类转录因子数据库中搜索可能存在的顺式结构;利用SAGE和GEO数据库对影响lrp16基因表达的相关药物作用进行分析。结果发现,lrp16基因在长度为3000bp的启动子区内,在负向表达调控区域存在多个顺式结构,其中包括T-Ag、PU.1、c-Ets、XPF-1、AP2αA、IL6-6RE和RAR。培养的体外细胞系在激素类物质皮质酮、他莫昔芬、毛喉素或去氧肾上腺素、炎性细胞因子IL4或TNFα或化疗药物5-氟尿嘧啶的作用下,lrp16基因的表达水平明显下降。结论:T-Ag、PU.1、c-Ets、XPF-1、AP2αA、IL6-6RE和RAR等转录因子可能抑制lrp16基因的表达;激素类物质皮质酮、他莫昔芬、毛喉素或去氧肾上腺素,炎性细胞因子IL6、IL4或TNFα,或化疗药物5-氟尿嘧啶可能具有抑制lrp16基因表达的作用。

The main purpose of the this study was to find the candidate cis-elements in negative regulation region throngh analysing the DNA sequences of lrp16 gene promoter so as to provide the experimental basis for screening drugs with inhibitory effect on lrp16 gene expression. The open reading frame（ORF） sequences in uncoding DNA and mRNA sequences of 5＇flanking region in lrp16 gene were cloned by the data in GeneBank and Internet ; the possibly existing ciselement in thsi region was searched in databank of human transcriptional factor by using TESS and Genomax online promoter analysis software; the drugs related to inhibition of lrpl6 gene expression were screened by using SAGE and GEO databank. The results showed that there were many cis-elements in the negative regulation region, including T-Ag, PU. 1, c-Ets, XPF-1, P2 etA, IL6-6RE and RAR. In cultured cell lines, hormone or its inhibitor such as corticosteroid, tamoxifen, forskolin, phenylephrine, inflammatory factors such as IFNγ/and TNFα, and chemotherapeutics 5-fluorouracil could down-regulate the lrp16 gene expression as compared with absent ones. It is concluded that cis-elements including T-Ag, PU- 1, c-Ets, XPF-1, P2 αA, IL6-6RE and RAR may inhibit lrp16 expression and hormone or its inhibitor such as corticosteroid, tamoxifen, forskolin, phenylephrine, inflammatory factors such as IL6, IFN-γ and TNFα, and chemotherapeutics 5-fluorouracil may participate in the regulation of lrp16 gene expression in negative manner.