Description: The ERalpha mRNA has a long 3' UTR of about 4.3 kb, which has been reported to reduce mRNA stability and which bears evolutionary conserved miRNA target sites, suggesting that it might be regulated by miRNAs. We have performed a comprehensive and systematic assessment of the regulatory role of all miRNAs that are predicted to target the 3' UTR of the ERalpha mRNA. We found that miR-22 represses ERalpha expression most strongly and by directly targeting the ERalpha mRNA 3' UTR. Of the three predicted miR-22 target sites in the 3' UTR, the evolutionary conserved one is the primary target. miR-22 overexpression leads to a reduction of ERalpha levels, at least in part by inducing mRNA degradation, and compromises estrogen signaling as exemplified by its inhibitory impact on the ERalpha-dependent proliferation of breast cancer cells. |
