dc.contributor.author | Khan, Sonja | |
dc.contributor.author | Wall, Deirdre | |
dc.contributor.author | Curran, Catherine | |
dc.contributor.author | Newell, John | |
dc.contributor.author | Kerin, Michael J | |
dc.contributor.author | Dwyer, Róisín M. | |
dc.date.accessioned | 2018-09-20T16:13:08Z | |
dc.date.available | 2018-09-20T16:13:08Z | |
dc.date.issued | 2015-05-02 | |
dc.identifier.citation | Khan, Sonja; Wall, Deirdre; Curran, Catherine; Newell, John; Kerin, Michael J; Dwyer, Roisin M (2015). Microrna-10a is reduced in breast cancer and regulated in part through retinoic acid. BMC Cancer 15 , | |
dc.identifier.issn | 1471-2407 | |
dc.identifier.uri | http://hdl.handle.net/10379/12250 | |
dc.description.abstract | Background: MicroRNAs (miRNAs) are short non-coding RNA molecules that play a critical role in mRNA cleavage and translational repression, and are known to be altered in many diseases including breast cancer. MicroRNA-10a (miR-10a) has been shown to be deregulated in various cancer types. The aim of this study was to investigate miR-10a expression in breast cancer and to further delineate the role of retinoids and thyroxine in regulation of miR-10a.
Methods: Following informed patient consent and ethical approval, tissue samples were obtained during surgery. miR-10a was quantified in malignant (n = 103), normal (n = 30) and fibroadenoma (n = 35) tissues by RQ-PCR. Gene expression of Retinoic Acid Receptor beta (RAR beta) and Thyroid Hormone receptor alpha (THR alpha) was also quantified in the same patient samples (n = 168). The in vitro effects of all-trans Retinoic acid (ATRA) and L-Thyroxine (T-4) both individually and in combination, on miR-10a expression was investigated in breast cancer cell lines, T47D and SK-BR-3.
Results: The level of miR-10a expression was significantly decreased in tissues harvested from breast cancer patients (Mean (SEM) 2.1(0.07)) Log(10) Relative Quantity (RQ)) compared to both normal (3.0(0.16) Log(10) RQ, p < 0.001) and benign tissues (2.6(0.17) Log(10) RQ, p < 0.05). The levels of both RAR beta and THR alpha gene expression were also found to be decreased in breast cancer patients compared to controls (p < 0.001). A significant positive correlation was determined between miR-10a and RAR beta (r = 0.31, p < 0.001) and also with THRa (r = 0.32, p < 0.001). In vitro stimulation assays revealed miR-10a expression was increased in both T47D and SK-BR-3 cells following addition of ATRA (2 fold (0.7)). While T-4 alone did not stimulate miR-10a expression, the combination of T-4 and ATRA was found to have a positive synergistic effect.
Conclusion: The data presented supports a potential tumour suppressor role for miR-10a in breast cancer, and highlights retinoic acid as a positive regulator of the microRNA. | |
dc.publisher | Springer Nature | |
dc.relation.ispartof | BMC Cancer | |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Ireland | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ | |
dc.subject | microrna (mirna) | |
dc.subject | microrna-10a (mir-10a) | |
dc.subject | breast cancer | |
dc.subject | retinoic acid (ra) | |
dc.subject | retinoic acid receptor beta (rar beta) | |
dc.subject | endogenous control genes | |
dc.subject | time quantitative pcr | |
dc.subject | cell differentiation | |
dc.subject | expression analysis | |
dc.subject | receptor-beta | |
dc.subject | rar-alpha | |
dc.subject | cyclin-b | |
dc.subject | mir-10a | |
dc.subject | carcinoma | |
dc.subject | proliferation | |
dc.title | Microrna-10a is reduced in breast cancer and regulated in part through retinoic acid | |
dc.type | Article | |
dc.identifier.doi | 10.1186/s12885-015-1374-y | |
dc.local.publishedsource | https://bmccancer.biomedcentral.com/track/pdf/10.1186/s12885-015-1374-y?site=bmccancer.biomedcentral.com | |
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