Abstract
Melatonin, a hormone secreted by pineal gland, exerts antimetastatic effects by reducing tumor cell proliferation, migration and invasion. MicroRNAs (miRNAs) are small, non-coding RNAs that play a crucial role in regulation of gene expression and biological processes of the cells. Herein, we search for a link between the tumor/metastatic-suppressive actions of melatonin and miRNA expression in triple-negative breast cancer cells. We demonstrated that melatonin exerts its anti-tumor actions by reducing proliferation, migration and c-Myc expression of triple negative breast cancer cells. By using Taqman-based assays, we analyzed the expression levels of a set of miRNAs following melatonin treatment of triple negative breast cancer cells and we identified 17 differentially expressed miRNAs, 6 down-regulated and 11 up-regulated. We focused on the anti-metastatic miR-148b and the oncogenic miR-210 both up-regulated by melatonin treatment and studied the effect of their modulation on melatonin-mediated impairment of tumor progression. Surprisingly, when miR-148b or miR-210 were depleted in triple-negative breast cancer cells, using a specific miR-148b sponge or anti-miR-210, melatonin effects on migration inhibition and c-myc downregulation were still visible suggesting that the increase of miR-148b and miR-210 expression observed following melatonin treatment was not required for the efficacy of melatonin action. Nevertheless, ours results suggest that melatonin exhibit a compound for metastatic trait inhibition, especially in MDA-MB-231 breast cancer cells even if a direct link between modulation of expression of certain proteins or miRNAs and melatonin effects has still to be established.
Highlights
Breast cancer is the most common type of cancer, and the second major cause of death in women worldwide [1]
In order to verify the antiproliferative effect of melatonin, MDA-MB-231 and MCF-7 cells were treated with 100 nM or 1 mM of melatonin for 24, 48, 72, 96 and 120 h
The results showed a statistically significant inhibitory effect on proliferation was observed only following melatonin treatment (1 mM) at 48 h for Estrogen Receptor (ER)positive MCF-7 cell line and at 72 h for ER-negative MDA-MB-231 cell line (Fig 1A)
Summary
Breast cancer is the most common type of cancer, and the second major cause of death in women worldwide [1]. The high mortality rate due to this neoplasm is intrinsically related to the occurrence of metastasis, which affects more than 90% of the patients. The early diagnosis and the introduction of more effective treatments have allowed. Melatonin action on triple-negative breast cancer cells the decrease in deaths and have improved the quality of life of patients with the disease [2]. The progression of breast cancer depends on the ability of cells to invade and colonize distant sites [3]. Dissemination of tumor cells is a complex multi-step process, including detachment of primary tumor cells, invasion of the local tumor microenvironment, survival in the circulation and extravasation in other tissues [4]
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