Figure 1

Schematic overview of miRNA processing and functions in cancer. Transcription from miRNA genes is under the regulation of transcription factors (TF) that respond to multiple signals and can also be epigenetically controlled. miRNA genes are transcribed by RNA polymerase II to produce a long nucleotide sequence, the pri-miRNA, which is cleaved by Drosha, a RNAse III endonuclease that recognizes internal hairpin structures. The resulting miRNA precursors (pre-miRNAs) of approximately 70 nucleotides are actively exported by Exportin-5 into the cytoplasm. Once in the cytoplasm, the pre-miRNAs are further digested by Dicer (another RNAse III endonuclease), which yields 21 to 22 nucleotide dsRNAs with two nucleotide overhangs (the miRNA* species is a rare non-miRNA cleavage product). Single strands from these dsRNAs associate with several members of the Argonaute (AGO) protein family to form the RNA induced silencing complex (RISC). The mRNA segments that miRNAs bind seem to be mostly in the 3' UTRs. Overexpression (up arrow) of a miRNA could result in downregulation of a tumor suppressor, or underexpression (down arrow) of a miRNA could lead to upregulation of an oncogene. These events thus promote cell proliferation, decrease apoptosis and stimulate angiogenesis, leading to tumorigenesis.