miRNAs as Regulators of Oncogene Expression
To address whether specific miRNAs might be participating in cancer through the mis-regulation of oncogenes, we scanned the 3' untranslated regions (UTRs) of 150 well-known oncogenes for sequences with significant homology to the miRNAs identified in our microarray analysis. We selected potential target sites based on two criteria:
(1) Perfect complementarity between positions 2-9 of the miRNA and the oncogene. This miRNA core sequence has been identified as critical to the activities of miRNAs and the known miRNA target sites have essentially 100% complementarity at this site .
(2) Overall Tm of the miRNA/mRNA interaction. In addition to the core sequence, overall binding stability between miRNAs and mRNAs has been shown to be an important indicator of miRNA activity .
As seen in Figure 4, potential target sites in the 3'
UTRs of known oncogenes were identified for all of the miRNAs that were
observed to be routinely differentially expressed in tumor samples. Interestingly,
KRAS2, MYCL1, and CBL have multiple predicted miRNA binding sites which
could provide the cooperative miRNA binding that has been implicated as
an important factor in miRNA regulation [6, 7]. Many of the genes listed
in Figure 4 become oncogenic when they are over-expressed, thus it is
conceivable that reduced expression of a miRNA could lead to up-regulation
of one or more oncogen