miR-28 expression suppresses established human lymphomas. (A) Ramos BL cells were transduced with lentivirus encoding miR-28 or scramble RNA (control), and cells were injected subcutaneously, without induction, into NSG mice. Xenografts were left to establish for 21 days (until reaching ∼250 mm3), and miR-28 expression was then induced by Dox in the drinking water. Graphs show volumes of individual tumors and mean values at the indicated times before (−Dox) and after (+Dox) Dox administration (supplemental Figure 5B). (B) Tumor weights of miR-28 and control xenografts at 18 days after Dox treatment. (C) Intratumor administration with synthetic miR-28 mimic suppresses established BL tumors. Wild-type Ramos cells were injected subcutaneously into NSG mice; after xenografts were established (tumor volume >200 mm3), synthetic miR-28 mimic (blue bars) or scrambled control mimics (red bars) were administered intratumorally (supplemental Figure 5C). Graphs show tumor volumes at the indicated times in xenografts before and after treatment with 0.1 nmol (left) or 0.5 nmol (right) of miRNA mimic. (D) Endpoint-to-pretreatment volume ratios for the xenografts in panel C. (E) Ramos xenografts were established as in panel C and mice were treated by intravenous administration of 7 nmol miR-28 mimic (blue) or scrambled mimics (control, red circles) (supplemental Figure 5D). The graph shows tumor volumes at the indicated times. Each circle corresponds to an independent tumor. *P < .05; **P < .01, unpaired Student t test.
