miR-379 Regulates Cyclin B1 Expression and Is Decreased in Breast Cancer
Date
2013Author
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 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).
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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) 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.