The role of melatonin on miRNAs modulation in triple-negative breast cancer cells

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.

Effects of physiological deficits in pineal melatonin on Triple Negative Breast Cancer

“…Assessment of the effect of melatonin on 4t1 cells in vitro was intended to identify any effect on tumor cell status (ROR score) and suggest mechanisms mediating effects of melatonin. The lack of melatonin effect on survival of 4t1 cells in vitro, was consistent with one study of MDA-MB-231 and HCC-70 TNBC cells, but different from a later study of MDA-MB-231 cells [22,23]. However, there was a clear effect of melatonin on gene expression.…”

“…Further, an effect of melatonin on TNBC cells is also supported experimentally. In vitro, melatonin has an oncostatic effect on TNBC cell invasiveness and proliferation [22,23]. In vivo, extremely high doses of exogenous melatonin inhibit TNBC xenograft growth, and have oncostatic effects on tumor microenvironment, especially immune and angiogenic markers [24,25].…”

Zinc and melatonin supplementation ameliorates brain cortex tissue damage in DMBA-induced breast cancer in rats

“…The role of melatonin produced and secreted by the pineal gland, as an anti-carcinogenic agent has been extensively investigated in the past few decades (9). Melatonin has been evaluated in various types of cancer, especially breast carcinoma (10).…”

“…While melatonin inhibits tumor growth by reducing cell proliferation, it also has anti-metastatic, pro-apoptotic, anti-angiogenic, antioxidant/anti-mutagenic and immuno-enhancing effects (9, 10). These effects of melatonin make it an excellent agent to reduce the risk of carcinogenesis in humans (9,10).…”

A meta‐analysis of microRNA networks regulated by melatonin in cancer: Portrait of potential candidates for breast cancer treatment

“…We initially performed a systematic meta-analysis to identify miRNA expression profiles targeted by melatonin in experimentally relevant studies. Based on the design criteria for eligibility ( Figure 1), 14 studies [47][48][49][50][51][52][53][54][55][56][57][58][59][60] were selected to investigate the miRNAs expression changes induced by melatonin treatment (Table S1). Among the 46 differentially expressed miRNAs, 29 were upregulated, and 17 were downregulated (Table S2).…”