Abstract
BackgroundMicroRNAs (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.MethodsFollowing 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 (RARβ) and Thyroid Hormone receptor alpha (THRα) was also quantified in the same patient samples (n = 168). The in vitro effects of all-trans Retinoic acid (ATRA) and L-Thyroxine (T4) both individually and in combination, on miR-10a expression was investigated in breast cancer cell lines, T47D and SK-BR-3.ResultsThe level of miR-10a expression was significantly decreased in tissues harvested from breast cancer patients (Mean (SEM) 2.1(0.07)) Log10 Relative Quantity (RQ)) compared to both normal (3.0(0.16) Log10 RQ, p < 0.001) and benign tissues (2.6(0.17) Log10 RQ, p < 0.05). The levels of both RARβ and THRα 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 RARβ (r = 0.31, p < 0.001) and also with THRα (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 T4 alone did not stimulate miR-10a expression, the combination of T4 and ATRA was found to have a positive synergistic effect.ConclusionThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1374-y) contains supplementary material, which is available to authorized users.
Highlights
MicroRNAs 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
MicroRNAs are an important class of short non-coding RNA molecules proven to have a critical role in mRNA cleavage or decay [1]. miRNAs play crucial roles in a variety of physiological as well as pathological processes including breast cancer [2]
Levels of miR-10a were significantly decreased in breast cancer tissues (n = 103, 2.3(0.08) Log10 RQ) compared to both normal (n = 30, 3.1(0.17) Log10 RQ, p < 0.001) and fibroadenoma tissues (n = 35, 2.9(0.15) Log10 RQ, p < 0.001, Figure 1). miR-10a expression was further stratified based on patient clinicopathological details
Summary
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. A study by Pogribny et al [18] showed higher expression of miR-10a in breast cancer MCF-7 cell lines with an inbuilt resistance to cisplatin. This analysis identified a potential role for miR-10a in the regulation of cellular proteins, including homeobox family HOXD10, tumour suppressor p27 and ER-alpha (ERα) [18]. A global miRNA profiling study revealed miR-10a to be involved in inhibition of HOXD4 expression in breast cancer cell lines [8]
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