miRNAs in ovarian cancer: A systems approach (mRNA data)

MicroRNAs (miRNAs) are short (~22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases including cancer. We report the results of a systems analysis of miRNA regulation in ovarian cancer. We found that 33 miRNAs are up-regulated and 9 down-regulated in CEPI relative to OSE (p<0.01, 2 fold change). Of these, 12 were previously annotated miRNAs (Sanger miRBase) of which 9 are up-regulated and 3 are down-regulated in CEPI relative to OSE. Current models predict that changes in levels of miRNAs will be inversely correlated with changes in the levels of targeted mRNAs due to miRNA regulation. This predicted inverse correlation held for only ~9% of predicted target mRNAs. Computational analyses indicate the unexpected low inverse correlation may be at least partially explained by variation in the number of miRNA binding sites within the 3 UTRs of targeted mRNAs and by miRNA-mediated changes in levels of transcription factors that can exert overriding trans-regulatory controls on target loci.

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Shahab SW, Matyunina LV, Mezencev R, Walker LD, Bowen NJ, Benigno BB, McDonald JF