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
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 (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.
The 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.
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.