Transcription profiling by array of human malignant melanoma cell line, A375, following interferon-gamma-induced gene transcription

MicroRNAs are major regulators of post-transcriptional gene regulation. Even small changes in miRNA levels may have profound consequences for the expression levels of target genes. Hence, miRNAs themselves need to be tightly, albeit dynamically, regulated. Here, we investigated the dynamic behaviour of miRNAs over a wide time range following transcriptional activation of melanoma cells by interferon-? (IFN-?), which activates the transcription factor STAT1. By applying several software packages for analyses, visualisation and identification of differentially expressed miRNAs derived from time-series microarray experiments, 8.9% (98) of 1102 miRNAs appeared to be directly or indirectly regulated by STAT1. Focussing on distinct dynamic expression patterns, we found that the majority of differentially expressed miRNAs were up-or down-regulated in the intermediate time range (24 h - 48 h), one (miR-27a*) was up-regulated early (already at 18 h), while none reacted late (after 72 h – 96 h). Expression of individual miRNAs was altered gradually over time or it abruptly increased between two time points. Furthermore, we have observed co-ordinated dynamic transcription of several clustered miRNAs. However, we also detected that some of those can be regulated independently of their genetic cluster. Most interestingly, several “star” or passenger strand sequences were specifically regulated over time while their “guide” strands were not.