MiR-9: A Potential Therapeutic Target for Invasive Breast Cancer

An estimated 200,000 new cases of invasive breast cancer were diagnosed in the United States in 2009. Metastasis of breast cancer occurs when cells break away from the primary tumor and invade other tissues. Breast cancer cells can metastasize to the brain, the lungs, to bone, and various other organs. This process is thought to occur in the later stages of cancer progression and is associated with mortality. A new study published in Nature Cell Biology characterized the contribution of a micro RNA (miRNA), specifically miR-9, in breast cancer motility.

The authors studied miR-9, as it was implicated in a previous study to be elevated in invasive breast cancer cells. Over-expression of miR-9 in breast cancer cells led to a decrease in E-cadherin, an inhibitor of migratory signaling. Interestingly, the over-expression of miR-9 led to an increase in cellular migration that could be reversed by the over-expression of E-cadherin. Decreased E-cadherin levels by miR-9 also increased gene expression of VEGF, a gene product implicated in angiogenesis and metastasis.

Injecting breast cancer cells into mice, such as those of the SUM149 cell line used by the authors, leads to in vivo tumor formation. Exogenous expression of miR-9 in these cells increased tumor size, angiogenesis, and the degree of metastasis. Conversely, reducing miR-9 in invasive mouse mammary cancer cells reduced metastasis by 50% compared to injected control cells. This suggests that miR-9 may regulate breast cancer invasiveness and severity.

This study is significant in that it uncovers a potential therapeutic target for treating breast cancer. Potentially, an inhibitor of miR-9 would inhibit the metastasis of breast cancer when this miRNA is elevated. It is unclear if such an inhibitor would treat the primary tumor, but curbing its spread could prevent the complications associated with cancer metastasis. Inhibiting miRNAs is not a novel idea; as such an inhibitor is currently being developed to treat hepatitis-c infection. Although promising, further research is needed to verify that targeting this miRNA would be beneficial for use in breast cancer therapy.

References

Breast Cancer Facts & Figures 2009-2010. http://www.cancer.org/downloads/STT/F861009_final%209-08-09.pdf

Ma, L., et, al. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nature Cell Biology. 2010;12(3):247-56.