Figure 8.

Detection of altered miRNA signatures following manipulation of miRNA expression. In the top and bottom panels miRNAs (x-axis) are ranked in order of average target gene expression (y-axis) with, for clarity, only miR-122a and miR124 labeled, respectively. Following inhibition of miR-122 by an antagomir [13] the position of the miR-122 average target gene expression in liver moved from the left to right of those for all ranked miRNAs (upper panel). This was reflected in a reduced probability (y-axis) that miR-122a predicted target genes were under-expressed, whilst all other miRNA effects remained relatively unaltered by the miR-122a antagomir (red versus dashed grey line in center left panel). Conversely, overexpression of miR-124 for 24 hours in the HepG2 cell line [12] caused miR-124 target gene expression to change from significantly highly over-expressed to significantly under-expressed (bottom panel). The selective drop in expression of miR-124 target gene expression is shown in the center right panel (this is apparent for the miR-122a and miR-122u isoforms present in the version of TargetScan used for this analysis). Whilst the data in this Figure are from analysis of mean absolute expression, the alternative methods produced similar results (data not shown).