Mir-379 regulates cyclin b1 expression and is decreased in breast cancer
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2013-07-10Author
Khan, Sonja
Brougham, Cathy L.
Ryan, James
Sahrudin, Arisha
O’Neill, Gregory
Wall, Deirdre
Curran, Catherine
Newell, John
Kerin, Michael J.
Dwyer, Róisín M.
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Khan, Sonja; Brougham, Cathy L. Ryan, James; Sahrudin, Arisha; O’Neill, Gregory; Wall, Deirdre; Curran, Catherine; Newell, John; Kerin, Michael J.; Dwyer, Roisin M. (2013). Mir-379 regulates cyclin b1 expression and is decreased in breast cancer. PLoS ONE 8 (7),
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Abstract
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) Log(10) Relative Quantity (RQ)) compared to normal breast tissues (2.6 (0.16) Log(10) 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.