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• Khan, S., Brougham, C. L., Ryan, J., Sahrudin, A., O’Neill, G., Wall, D., Curran, C., Newell, J., Kerin, M.J., Dwyer, R. M.
Plos One
miR-379 Regulates Cyclin B1 and is decreased in Breast Cancer
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MicroRNA, Breast Cancer, tumour suppressor, Cyclin B1
MicroRNAs are small non-coding RNA molecules that control gene expression post-transcriptionally, and are known to be altered in many diseases including breast cancer. The aim of this study was to determine the relevance of miR-379 in breast cancer. miR-379 expression was quantified in clinical samples including tissues from breast cancer patients (n=103), healthy controls (n=30) and patients with benign breast disease (n=35). The level of miR-379 and its putative target Cyclin B1 were investigated on all breast tissue specimens by RQ-PCR. Potential relationships with gene expression and patient clinicopathological details were also determined. The effect of miR-379 on Cyclin B1 protein expression and function was investigated using western blot, immunohistochemistry and proliferation assays respectively. Finally, the levels of circulating miR-379 were determined in whole blood from patients with breast cancer (n=40) and healthy controls (n=34).   The level of miR-379 expression was significantly decreased in breast cancer (Mean(SEM) 1.9(0.09)Log10 Relative Quantity(RQ)) compared to normal breast tissues (2.6(0.16) Log10 RQ, p<0.01).  miR-379 was also found to decrease significantly with increasing tumour stage. A significant negative correlation was determined between miR-379 and Cyclin B1 (r=-0.31, p<0.001). Functional assays revealed reduced proliferation (p<0.05) and decreased Cyclin B1 protein levels following transfection of breast cancer cells with miR-379. Circulating miR-379 was not significantly dysregulated in patients with breast cancer compared to healthy controls (p=0.42). This data presents miR-379 as a novel regulator of Cyclin B1 expression, with significant loss of the miRNA observed in breast tumours.
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