Figure 6
The miR-29 family is involved in multiple cellular processes. UV-radiation triggers the recruitment of macrophages to the skin, which secrete cytokines like interferon gamma (IFN-γ). By binding to its receptors, IFN-γ signals through the Jak/STAT pathway triggering subsequent activation of STAT1, which then binds to GAS-elements in the promoter region of target genes and initiates their transcription. IFN-γ-induced, STAT1-dependent up-regulation of miR-29 causes a down-regulation of CDK6, a novel miR-29 target gene in melanoma, which plays a crucial role in cell cycle G1/S-transition and thus growth control of cancer cells. The cell cycle inhibitor p16INK4A is often deleted in melanoma and its function (inhibition of CDK6) might be compensated by miR-29a/b. IFN-γ-activating transcription factors T-bet and Eomes and IFN-γ itself are also targeted by miR-29.