MicroRNA and gene expression analysis of melatonin-exposed human breast cancer cell lines indicating involvement of the anticancer effect

Abstract

MicroRNAs (miRNAs) are small, noncoding RNAs that play a crucial role in regulation of gene expression. Recent studies have shown that miRNAs implicated in initiation and progression of various human cancers, including breast cancer and also analysis of miRNA expression profiles in cancer provide new insights into potential mechanisms of carcinogenesis. Melatonin, N-acetyl-5-methoxytryptamine, is synthesized by the pineal gland in response to the dark/light cycle and has been known to act as a synchronizer of the biological clock. Melatonin has a variety of therapeutic effects, such as immunomodulatory actions, anti-inflammatory effects, and antioxidant actions. Furthermore, melatonin is reported to have an anticancer function including suppression of the metabolism of tumor cells and induction of tumor suppressor genes in cancer cells, including breast cancer cells. In this study, we determined whether miRNAs play a role in regulation of various gene expression responses to melatonin in MCF-7 human breast cancer cells. We examined whole-genome miRNA and mRNA expression and found that 22 miRNAs were differentially expressed in melatonin-treated MCF-7 cells. We further identified a number of mRNAs whose expression level shows a high inverse correlation with miRNA expression. The Gene Ontology (GO) enrichment analysis and pathways analysis were performed for identification of the signaling pathways and biological processes affected by differential expression of miRNA and miRNA-related genes. Our findings suggested that melatonin may modulate miRNA and gene expression as an anticancer mechanism in human breast cancer cells.

Interactions of Melatonin and MicroRNAs

“…In hypoxic PC-3 prostate cancer cells, melatonin was shown to inhibit angiogenesis, an effect of importance to cancer growth that was concluded to be mediated by miR-3195 and miR-374b [39]. A more detailed study in MCF-7 breast cancer cells revealed alterations in the expression of 22 miRNAs by either 1 nM or 100 nM melatonin [40]. Twelve miRNAs were significantly upregulated and ten others downregulated.…”

“…Twelve miRNAs were significantly upregulated and ten others downregulated. According to the analysis of their 5'-utr sequences, the 22 miRNAs should be capable of targeting the remarkable number of 2029 mRNAs [40].…”

Melatonin, Noncoding RNAs, Messenger RNA Stability and Epigenetics—Evidence, Hints, Gaps and Perspectives

“…In MCF-7 cells treated with 100 nM melatonin, 22 miRNAs were differentially expressed compared to controls; 12 of them were up-regulated and 10 down-regulated [171]. At the near-physiological concentration of 1 nM, four up-regulated and one down-regulated miRNAs were detected.…”

Emerging roles of MicroRNAs in osteonecrosis of the femoral head

“…[18][19][20][21] Previous studies have indicated that miRNAs play crucial roles in diverse physiological processes, including development, cell proliferation, differentiation, metabolism, migration and apoptosis. [22][23][24][25] Increasing evidence also suggested that miRNAs can regulate bone development and regeneration and are directly involved in the pathogenesis of numerous of orthopaedic conditions, such as intervertebral disc degeneration, osteoarthritis, osteoporosis and osteosarcoma. [26][27][28][29] Importantly, the roles of microRNAs in many of these orthopaedic conditions have been critically assessed.…”