MicroRNAs Indirectly Regulate Other MicroRNAs in Ovarian Cancer Cells

Abstract

MicroRNAs (miRNAs) are a class of regulatory RNAs that control the expression of genes critical to cell function. Ectopic expression of miRNAs has been shown to result in genome-wide changes in patterns of gene expression. While the reasons for these global alterations in gene expression patterns have been attributed to the ability of miRNAs to target multiple genes, and/or to induce indirect effects downstream of target genes, the molecular basis of indirect effects of miRNA regulation remains poorly understood. In this study, we demonstrate the potential of miRNAs to regulate other miRNAs. Using miRNA microarray analysis, we show that over 70 different miRNAs are differentially expressed (≥1.4 fold, FDR≤5%) in human ovarian cancer cells after transfection with a single miRNA (miR-7). We present evidence that a major component of miR-7 induced changes in levels of miRNAs is the indirect consequence of miR-7 mediated alterations in levels of protein coding genes (e.g., transcription and splicing factors) that exert trans-regulatory control on miRNAs.