Figure 2.

Genetic factors affecting microRNA expression and function in cancer. (A) Single nucleotide polymorphisms (SNPs) affecting the microRNA (miRNA) gene can alter miRNA production through impeding processing by ribonuclease III enzyme Drosha or Dicer, by alteration in binding and cleavage sites (red triangles). SNPs can also change the seed sequence, leading to a different targetome for the miRNA and thus altered post-translational regulation. (B) In addition to mutations in the miRNA gene itself, the promoter and transcription-enhancing region of miRNA genes can also acquire SNPs. This can impair binding of transcription factors, such as MYC, leading to decreased transcription of the miRNA gene. (C) Epigenetic modifications of the miRNA gene can also affect miRNA expression. Hypermethylation of the miRNA promoter, as well as histone methylation at H3K27, both repress transcription. On the other hand, histone methylation at H3K4 is associated with transcriptional activation of miRNA genes. (D) Some miRNA genes do not have a promoter of their own, which makes them dependent on their host gene. When the host gene promoter is hypermethylated, expression of the miRNA/mirtron is decreased as well. (E) Copy number variations are large chromosomal changes, which include deletions of miRNA genes, or translocations to other positions in the genome, creating gene amplification. When a part of the chromosome is amplified or deleted, the level of miRNA gene expression is decreased or increased, respectively (Created with BioRender.com).