Study looks at use of melatonin in the treatment of breast cancer

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A Brazilian study published in the Journal of Pineal Research describes a group of genes potentially regulated by the hormone melatonin in some types of cancer, especially breast cancer.

Known as the sleep hormone because its functions include regulating the sleep-wake cycle, melatonin has been shown to have anti-tumor properties in laboratory trials. Evidence presented in the scientific literature suggests that low levels of melatonin are associated with a heightened risk of cancer. A possible explanation is that the hormone contributes to the modulation of gene expression and may intensify the activity of tumor suppressor genes, according to the study.

To identify molecular markers that serve as guides for cancer treatment, the researchers first conducted a study based on meta-analysis to find out how melatonin regulates microRNA expression in breast, head and neck, liver, stomach, prostate, central nervous system, and colorectal cancer.

Meta-analysis entails a systematic review of the literature using statistical methods to integrate the results of published research on the same subject. MicroRNAs are small RNA molecules that do not encode proteins but perform a regulatory function in the genome, controlling gene expression and hence several cellular processes.

Next, the researchers used bioinformatics to identify pathways associated with the hormone’s action on tumor cells, basing their analysis on the association between these microRNAs and their regulatory targets. Regulatory and molecular networks were generated and analyzed. As a result, they were able to understand how melatonin works in several cellular signaling pathways. 

Breast cancer was associated with the most genes and microRNAs in this first stage of the study, so the researchers compared the target genes for the microRNAs concerned with the data obtained by RNA-sequence analysis of breast tumors in mice treated with melatonin. RNA-sequence uses next-generation sequencing technology to study the expression of several genes at the same time and hence to obtain the entire transcriptome, such as the complete set of RNA molecules expressed in a tissue.

In the animals treated with 40 milligrams of melatonin, there was an enrichment of signaling pathways related to the immune system and apoptosis, and a reduction of pathways associated with tumor aggressiveness and metastasis, according to the study. The group also investigated certain proteins, including transcription factors and kinases, that are active in such processes as transcription and the cellular cycle. The researchers said genes regulated by melatonin in breast cancer are potential targets for the treatment of the disease. 

According to the authors, the results can be used to guide future personalized therapies for the disease.