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11, 2020 // -- In a recent study published in the international journal Journal of Pineal Research, scientists from Brazil and the United States described a group of genes that are potentially regulated by melatonin in certain cancer types, especially breast cancer, and the results may be used to help develop new individualized therapies for the disease.
type of tumor appears to be directly related to levels of melatonin produced by cells, and understanding the mechanisms at which the hormone affects molecular signals at genetic levels may help scientists develop individual therapies based on melatonin, said luiz Gustavo Chuffa, a researcher at the University of Hong Kong.
Melatonin is commonly known as "sleep hormone" because its function includes regulating the body's wake cycle, and in laboratory trials, researchers have found that melatonin has anti-tumor properties;
Photo Source: Melatonin levels are low in most tumor cells in NCI/NIH, but laboratory results show that melatonin therapy can increase tumor cell death and reduce tumor cell proliferation, which is important to avoid tumor progression and metastasis.
Now that researchers are conducting clinical trials to assess whether melatonin can be used to treat cancer, researchers have developed special treatments for different breast cancer subsypes, some of which may respond better to melatonin-based alternative therapies, while others may not.
Looking for targeted genes to identify molecular markers that could serve as guidelines for cancer therapy, the researchers first conducted a comprehensive analysis of how melatonin regulates the expression of microRNA molecules in a variety of regulated, including breast, head and neck, liver, stomach, prostate, central nervous system and colorectal cancers.
Comprehensive analysis requires a systematic review of the literature using statistical methods to integrate several studies that have been published on the same topic; microRNAs are small RNA molecules that do not encode proteins but play a regulatory role in the genome to control gene expression and multiple cellular processes.
, we found 14 studies that revealed a link between melatonin and microRNA expression changes, and 46 microRNA molecules that changed expression for the seven cancers we looked at,' said
researcher Chuffa.
The researchers then used bioinsynatics to identify paths associated with the role of hormones in tumor cells based on an analysis of the association between microRNAs and their regulatory targets, and then they generated and analyzed a variety of regulatory and molecular networks.
further analysis, the researchers identified 46 target genes for expression changes in microRNAs.
So researchers can understand how melatonin works in a variety of cellular signaling paths, and melatonin-targeted genes are associated with important biological processes in cancer, such as cell circulation regulation, cell death, migration, and aging.
melatonin appears to have a stronger effect on a variety of cancers, including breast, oral and stomach cancers, while microRNAs-induced changes are less common for prostate, colorectal and glioblastoma.
researchers found that breast cancer was associated with the largest number of genes and microRNAs, and then compared the target genes of the associated microRNA with the results of RNA sequencing analysis of breast tumors in mice treated with melanoma;
Chuffa said that in animal models treated with 40mg of melatonin, signaling paths associated with the immune system and apoptosis were abundant, while paths associated with tumor invasiveity and metastasis were reduced.
, the researchers looked at specific proteins (transcription factors, kinases, etc.) that are active during processes such as transcription and cell cycles, with the goal of finding common targets in the public database of cellular processes and breast cancer.
The melatonin-regulated gene in breast cancer may be a potential target for the development of new breast cancer therapies; melatonin is a multitaste molecule that works on a variety of cell substrates, so researchers are now delving into how melatonin affects the expression of microRNA to identify the regulatory mechanisms of cells.
original source: Luiz Gustavo de Almeida Chuffa, Robson Francisco Carvalho, Luis Antônio Justulin, et al. A meta‐analysis of microRNA networks regulated by melatonin in cancer: Portrait of potential candidates for breast cancer treatment, Journal of Pineal Research (2020). DOI:10.1111/jpi.12693。