Figure 7: The regulatory loop involving miR-17-92 and MYC maintains lymphoma homeostasis.

(a) A modest increase of MYC protein level restores growth rate of miR-17-19b-overexpressing cells. Growth rate of the cells is displayed as line plots, which are the mean±s.e.m. from three independent experiments. (b) Frequency of poly(A) site usage analysis for ‘regulated’ and ‘non-regulated’ miR-17 targets. The comparison between regulated and non-regulated targets reveals longer 3′ UTRs for the class of regulated targets, but only when they are co-regulated by MYC. A Mann–Whitney U test was used to determine statistical differences between the two distributions (*P≤0.05). (See related Supplementary Fig. 8). (c) Proposed model for miR-17-92 role in maintaining lymphoma homeostasis is schematized (modified from the study by Aguda et al.⁹). A ‘cancer zone’ is defined by a dynamic equilibrium between proliferation and apoptosis. During B cell lymphomagenesis, miR-17-92 antagonizes MYC-induced apoptosis by downregulation of Pten, operating as an oncogene. In full-blown lymphoma, instead, miR-17-92 inhibits cell cycle progression and increases apoptosis through a tight regulation of MYC expression and function, acting as a tumour suppressor.