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

• Published in: PloS one 2020-02, Vol.15 (2), p.e0228062-e0228062
• Main Authors: Ferreira, Lívia C, Orso, Francesca, Dettori, Daniela, Lacerda, Jéssica Z, Borin, Thaiz F, Taverna, Daniela, Zuccari, Debora A P C
• Format: Article
• Language: English
• Subjects: Analysis; Angiogenesis; Binding sites; Biochemistry; Biological activity; Biology and Life Sciences; Biotechnology; Breast; Breast cancer; c-Myc protein; Cancer cells; Cancer metastasis; Care and treatment; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Development and progression; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Genes; Health sciences; Hormones; Humans; Medicine and Health Sciences; Melatonin; Melatonin - pharmacology; Metastases; Metastasis; MicroRNA; MicroRNAs; MicroRNAs - genetics; Migration inhibition; miRNA; Modulation; Molecular biology; Myc protein; Non-coding RNA; Pineal gland; Proteins; Proto-Oncogene Proteins c-myc - metabolism; Research and Analysis Methods; Triple Negative Breast Neoplasms - pathology; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0228062

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.