Abstract B20: Breast cancer progression suppressor miR-290 targets breast cancer biomarker Arid4b

Several microRNAs (miRNAs) have been classified as metastasis regulators in breast cancer, yet few studies have examined how germline variations may promote metastasis via miRNA dysregulation. To explore this concept, highly metastatic MMTV-PyMT mice were crossed with 25 AKXD (AKR/J × DBA/2J) recombinant inbred strains to produce F1 progeny with varying metastatic indices. All mammary tumors in the F1 progeny were evaluated by miRNA microarray and correlated with metastatic index to produce miR-290 (containing mature miR-290-3p and miR-290-5p) as one of the top candidates. Further analysis showed miR-290-3p was downregulated in normal lung and breast tissue from highly metastatic AKR/J strains versus less metastatic DBA/2J strains, thereby supporting a germline component to miR-290 regulation. Next, when miR-290 was ectopically expressed in Mvt-1 and 6DT1, and orthotopically injected into FVB/N mice, a significant reduction in both mammary tumor burden and the number of pulmonary metastases was observed. Computational analysis identified breast cancer biomarker Arid4b as a top target of miR-290-3p, which was confirmed by luciferase reporter assay. In conclusion, these results suggest germline genetic changes may reduce miR-290 expression, in turn increasing Arid4b expression, to create a predisposition towards breast cancer progression. Citation Format: Natalie Goldberger, Renard Walker, Chang Hee Kim, Kent Hunter. Breast cancer progression suppressor miR-290 targets breast cancer biomarker Arid4b [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr B20.