Mechanisms of miRNA dysregulation in cancer. The example shown here to illustrate the different mechanisms has the miRNA located in the intron of a host gene containing 2 exons. (A) A miRNA may be underexpressed or overexpressed due to deletion (green bar) or gain (red bar) of the genomic locus containing the miRNA. (B) Mutation in the miRNA precursor that affects the processing of miRNA may lead to underexpression of the miRNA. (C) Transcriptional repression (eg, by MYC) or activation (eg, by p53) by transcription factors may lead to underexpression or overexpression of miRNA. (D) miRNA expression may be suppressed by promoter methylation. (E) A novel mechanism identified by Ballabio and colleagues where miRNA expression is suppressed by other miRNA inhibiting the expression of the host gene.