Intriguingly, miR-132 was previously shown to repress the expression of MeCP2 through direct interaction with the transcript 3′UTR (Klein et al., 2007). Moreover, as miR-132 and miR-212 share the same seed region, this suggests that miR-212 may similarly repress MeCP2. Based on these observations, we hypothesized that in addition to the inhibitory effects of MeCP2 on miR-212 expression described above, MeCP2 levels in turn may be repressed by miR-212. In other words, miR-212 and MeCP2 may be locked in a homeostatic relationship that serves to control miR-212 expression level and thereby influence vulnerability to cocaine addiction. Consistent with this hypothesis, we found that miR-212 overexpression profoundly decreased MeCP2 expression in cultured cells and in the striatum in vivo (Im et al., 2010). Hence, homeostatic interactions between miR-212 and MeCP2 may determine vulnerability to cocaine addiction.
