An integrated systems genetics screen reveals the transcriptional structure of inherited predisposition to metastatic disease

Mir216/217 are inherited metastasis suppressors. (A) Expression-phenotype correlations for Mir216a, Mir216b, and Mir217 in [AKXD_n × PyMT]F₁ tumors. Blue, yellow, and red points indicate AKXD sublines with respective weak, intermediate, and high metastatic propensities. (B) miR-eQTL analysis demonstrated peaks reaching genome-wide significance (red line) for Mir216a and Mir217 and reaching the “suggestive” threshold (gray line) for Mir216b. Consistent with a cis-eQTL, these peaks co-localize to the Mir216/217 locus on chromosome 11. Please refer to Supplemental Figure 31 for a detailed, high-resolution format of eQTL plots. (C) Ectopic expression of Mir216a, Mir216b, and Mir217 in 6DT1 cells. (D) Orthotopic implantation of 6DT1 cells expressing control miRNA, Mir216a, Mir216b, or Mir217. Mir216b and Mir217 expression reduced pulmonary metastasis by 79% and 80%, respectively (p_Mir216b = 0.011, p_Mir217 = 0.022; n = 10 mice per group). (*) P < 0.05.