miR-379 Regulates Cyclin B1 Expression and Is Decreased in Breast Cancer
Khan, Sonja Brougham, Cathy L. Ryan, James Sahrudin, Arisha O'Neill, Gregory Wall, Deirdre Curran, Catherine Newell, John Kerin, Michael J. Dwyer, Róisín M.
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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2013
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Article
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Khan S, Brougham CL, Ryan J, Sahrudin A, O'Neill G, Wall D, Curran C, Newell J, Kerin MJ, Dwyer RM (2013) 'miR-379 Regulates Cyclin B1 Expression and Is Decreased in Breast Cancer'. Plos One, 8 (7).
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) 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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10.1371/journal.pone.0068753
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Attribution-NonCommercial-NoDerivs 3.0 Ireland