Figure 1.Proposed mechanisms for avoidance of regulation by miRNAs in cancer cells.
We propose that cancers may
evolve to avoid regulation by miRNAs in order to enhance their tumorigenic
potential. This might occur through a variety of mechanisms: (I) combined
transcriptional/post-transcriptional FFL wiring, which may enhance the
repression of several co-regulated miRNAs, thereby facilitating the
expression of the mutual target genes; (II) global avoidance of miRNA
regulation via expression of shorter 3' UTRs [42]; (III) global reduction
in miRNA levels by impairing miRNA biogenesis in various ways, some of
which were shown to happen in tumors, such as inhibition of Drosha processing [39,40] and pre-miRNA nuclear retention [36]. All of these are suggested as
means that developing tumors may evolve to enhance proliferation and
increase genome instability.
