Identification of miR-290-3p and miR-290-5p as tumor and metastasis suppressors in breast cancer

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NCI	SIG/RNA/CYTOK-4

* FARE Award Winner

Authors

• N Goldberger
• R Walker
• CH Kim
• K Hunter

Abstract

Several microRNAs (miRNAs) have been classified as regulators of breast cancer metastasis, yet few studies have examined how germline genetic variations may dysregulate miRNAs. To explore this concept, MMTV-PyMT mice were crossed with 25 AKXD (AKR/J x DBA/2J) recombinant inbred strains to produce F1 progeny. The mammary tumors in the F1 progeny were evaluated by miRNA microarray and correlated with the metastatic index for each strain. Microarray analysis produced miR-290 as one of the top candidates (p = 0.014). When miR-290, containing both miR-290-3p and miR-290-5p, was ectopically expressed in the metastatic breast cancer cell line Mvt-1 and orthotopically injected into FVB/N mice, a 70% reduction in mammary tumor burden and a complete suppression of lung metastasis was observed. Next, the individual phenotypic effects of miR-290-3p and miR-290-5p were evaluated in vivo using Mvt-1 clones with either miR-290-3p or miR-290-5p upregulation. miR-290-5p reduced the number of pulmonary metastasis by 90% and mammary tumor burden by 60%, while miR-290-3p reduced the number of pulmonary metastases by 25% and mammary tumor burden by 90%. In conclusion, these results suggest germline genetic changes may reduce miR-290 expression, thereby creating a predisposition towards breast cancer development and metastasis.

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