title: miR-379 regulates cyclin B1 expression and is decreased in breast cancer.
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.
authors.affiliation: Discipline of Surgery, School of Medicine, National University of Ireland, Galway, Galway, Ireland.
authors.forename: Sonja
authors.initials: S
authors.lastname: Khan
authors.forename: Cathy L
authors.initials: CL
authors.lastname: Brougham
authors.forename: James
authors.initials: J
authors.lastname: Ryan
authors.forename: Arisha
authors.initials: A
authors.lastname: Sahrudin
authors.forename: Gregory
authors.initials: G
authors.lastname: O'Neill
authors.forename: Deirdre
authors.initials: D
authors.lastname: Wall
authors.forename: Catherine
authors.initials: C
authors.lastname: Curran
authors.forename: John
authors.initials: J
authors.lastname: Newell
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kerin
authors.forename: Roisin M
authors.initials: RM
authors.lastname: Dwyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D056744:Cyclin B1 / Q000235:genetics*; D005260:Female; D018226:Fibroadenoma / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: C534699:CCNB1 protein, human; D056744:Cyclin B1; C561022:MIRN379 microRNA, human; D035683:MicroRNAs