MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia.
MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia.
复制标题
DOI：
10.1371/journal.pone.0000116
复制
发表时间：
2006-12-27
期刊：
影响因子：
3.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Hua Z;Lv Q;Ye W;Wong CK;Cai G;Gu D;Ji Y;Zhao C;Wang J;Yang BB;Zhang Y
MicroRNA（miRNAs）是一类长度为20-24 nt的非编码RNA，主要通过转录后抑制或mRNA降解以序列特异性方式调控基因表达。miRNA的作用才刚刚开始被理解，但由于对miRNA调控基因的一般原理理解不足，对miRNA功能的研究受到限制。本研究以人鼻咽癌细胞系CNE细胞为研究对象，探讨miRNA对缺氧条件下VEGF等血管生成因子的调控作用，并探讨miRNA的基因调控原理。通过计算分析，96个miRNAs被预测为VEGF的假定调节因子。但是当我们分析CNE和其他四种表达VEGF的细胞系的miRNA表达谱时，我们发现这些miRNA中只有一部分可能参与VEGF的调节，并且VEGF可能受到不同miRNA的调节，这些miRNA是从不同细胞中的96种VEGF的假定调节miRNA中差异选择的。这些miRNAs中的一些还共同调节其他血管生成因子（差异调节和共同调节原理）。我们还发现，VEGF是由多个miRNA使用不同的组合，包括协调和竞争相互作用的调节。协调原理指出，在基因中具有独立结合位点的miRNAs可以产生协调作用，以增加miRNAs对该基因的抑制作用。相比之下，竞争性原理表明，当多个miRNA相互竞争共同的结合位点时，或者当功能性miRNA与假阳性miRNA竞争相同的结合位点时，miRNA的抑制作用可能会降低。通过竞争原理，不能直接抑制基因表达的假阳性miRNA有时可以在miRNA介导的基因调控中发挥作用。竞争原理、差异调节、多miRNA结合位点和假阳性miRNA可能是避免多靶点miRNA靶向基因之间不必要的交叉作用的有用策略。
MicroRNAs (miRNAs) are a class of 20–24 nt non-coding RNAs that regulate gene expression primarily through post-transcriptional repression or mRNA degradation in a sequence-specific manner. The roles of miRNAs are just beginning to be understood, but the study of miRNA function has been limited by poor understanding of the general principles of gene regulation by miRNAs. Here we used CNE cells from a human nasopharyngeal carcinoma cell line as a cellular system to investigate miRNA-directed regulation of VEGF and other angiogenic factors under hypoxia, and to explore the principles of gene regulation by miRNAs. Through computational analysis, 96 miRNAs were predicted as putative regulators of VEGF. But when we analyzed the miRNA expression profile of CNE and four other VEGF-expressing cell lines, we found that only some of these miRNAs could be involved in VEGF regulation, and that VEGF may be regulated by different miRNAs that were differentially chosen from 96 putative regulatory miRNAs of VEGF in different cells. Some of these miRNAs also co-regulate other angiogenic factors (differential regulation and co-regulation principle). We also found that VEGF was regulated by multiple miRNAs using different combinations, including both coordinate and competitive interactions. The coordinate principle states that miRNAs with independent binding sites in a gene can produce coordinate action to increase the repressive effect of miRNAs on this gene. By contrast, the competitive principle states when multiple miRNAs compete with each other for a common binding site, or when a functional miRNA competes with a false positive miRNA for the same binding site, the repressive effects of miRNAs may be decreased. Through the competitive principle, false positive miRNAs, which cannot directly repress gene expression, can sometimes play a role in miRNA-mediated gene regulation. The competitive principle, differential regulation, multi-miRNA binding sites, and false positive miRNAs might be useful strategies in the avoidance of unwanted cross-action among genes targeted by miRNAs with multiple targets.
登录
查看更多内容
影响因子：
14.9
作者：
Griffiths-Jones, S
通讯作者：
Griffiths-Jones, S
影响因子：
64.8
作者：
O'Donnell, KA;Wentzel, EA;Mendell, JT
通讯作者：
Mendell, JT
影响因子：
64.5
作者：
Lewis, BP;Shih, IH;Burge, CB
通讯作者：
Burge, CB
影响因子：
11.4
作者：
Koshiji, M;Kageyama, Y;Huang, LE
通讯作者：
Huang, LE
影响因子：
9.8
作者：
John B;Enright AJ;Aravin A;Tuschl T;Sander C;Marks DS
通讯作者：
Marks DS