Department of Biology, Universidade Estadual Paulista "Júlio de Mesquita Filho", São José do Rio Preto, São Paulo, Brazil.
Molecular Biotechnology Center (MBC), Department Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
PLoS One. 2020 Feb 3;15(2):e0228062. doi: 10.1371/journal.pone.0228062. eCollection 2020.
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.
褪黑素是由松果体分泌的一种激素，通过降低肿瘤细胞增殖、迁移和侵袭来发挥抗转移作用。microRNAs（miRNAs）是一种小的非编码 RNA，在基因表达调控和细胞的生物过程中起着关键作用。在这里，我们寻找褪黑素与三阴性乳腺癌细胞中 miRNA 表达之间的肿瘤/转移抑制作用之间的联系。我们证明褪黑素通过降低三阴性乳腺癌细胞的增殖、迁移和 c-Myc 表达来发挥其抗肿瘤作用。通过使用 Taqman 检测，我们分析了三阴性乳腺癌细胞经褪黑素处理后一组 miRNA 的表达水平，发现了 17 个差异表达的 miRNA，其中 6 个下调，11 个上调。我们关注了抗转移的 miR-148b 和致癌的 miR-210，它们都被褪黑素上调，并研究了它们的调节对褪黑素介导的肿瘤进展受损的影响。令人惊讶的是，当 miR-148b 或 miR-210 在三阴性乳腺癌细胞中被耗尽时，使用特定的 miR-148b 海绵或抗 miR-210，褪黑素对迁移抑制和 c-Myc 下调的作用仍然可见，这表明观察到的褪黑素处理后 miR-148b 和 miR-210 表达的增加对于褪黑素作用的疗效不是必需的。然而，我们的结果表明，褪黑素表现出一种抑制转移表型的化合物，特别是在 MDA-MB-231 乳腺癌细胞中，即使在某些蛋白质或 miRNA 的表达调节与褪黑素作用之间仍然需要建立直接联系。
