MicroRNAs Indirectly Regulate Other MicroRNAs in Ovarian Cancer Cells
Shubin W. Shahab
School of Biology, Georgia Institute of Technology, Atlanta, GA, USA and Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA
Lilya V. Matyunina
School of Biology, Georgia Institute of Technology, Atlanta, GA, USA and Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA and Ovarian Cancer Institute, Atlanta, GA, USA
Vinay K. Mittal
School of Biology, Georgia Institute of Technology, Atlanta, GA, USA and Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA
Lijuan Wang
School of Biology, Georgia Institute of Technology, Atlanta, GA, USA and Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA
Christopher G. Hill
School of Biology, Georgia Institute of Technology, Atlanta, GA, USA and Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA
L. DeEtte Walker
School of Biology, Georgia Institute of Technology, Atlanta, GA, USA and Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA and Ovarian Cancer Institute, Atlanta, GA, USA
John F. McDonald *
School of Biology, Georgia Institute of Technology, Atlanta, GA, USA and Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA and Ovarian Cancer Institute, Atlanta, GA, USA
*Author to whom correspondence should be addressed.
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.
Keywords: miRNA, ovarian cancer, systems biology, miR-7, NF-κB