Fig. 3

Model showing the interplay of microRNAs in senescence, proliferation and inflammation. MicroRNAs provide negative feedback of the RB pathway, the MAPK pathway and the NF-κΒ network. MiR-34a and miR-503 are predicted to target CCND1 and CDK4 to limit cell proliferation via the RB pathway. MiR-155 is predicted to target KRAS, miR-34a is predicted to target MEK1, whilst down stream targets of the MAPK pathway include SPRED1 (a predicted target of miR-503), SPRY1, SPRY2 and SPRY4 (predicted targets of miR-450b-5p) and FOS and ETS1 (predicted targets of miR-155). MicroRNAs that act as effectors and regulators of NF-κB include miR-146a, miR-155, miR-199a and miR-21. MiR-146a, miR-224 and miR-155 are predicted to target senescenceassociated genes and thus to regulate levels of inflammation