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Studies Can Direct the Use of Melatonin in the Treatment of Breast Cancer

Publicado em 08 dezembro 2020

Brazilian study published in Pineal Gland Research Journal Describes a group of genes that are potentially regulated by the hormone melatonin in several types of cancer, especially breast cancer. According to the author, the results can be used to guide future personalized treatments for the disease.

“Certain types of tumors appear to correlate directly with the amount of melatonin produced by cells. As a guideline for melatonin-based personalized treatment, how hormones affect molecular signaling at the genetic level. It is essential to understand, “Professor Luis Gustavo Chufa, Botukatu Institute for Biological Sciences (IBB-UNESP) at the State University of São Paulo, told Agência FAPESP.

The study was supported by FAPESP and was conducted in collaboration with researchers at the University of North Parana (UENP) in Brazil, the San Jose Dorio Preto Medical College (FAMERP), and the University of Texas Health Sciences Center in San Antonio, USA.

Known as a “sleep hormone” because its function involves regulation of the sleep-wake cycle, melatonin has been shown to have antitumor properties in laboratory studies. Evidence presented in the scientific literature suggests that low levels of melatonin are associated with an increased risk of cancer. A possible explanation is that hormones can contribute to the regulation of gene expression and, for example, increase the activity of tumor suppressor genes.

“Most tumor cells have low levels of melatonin, but laboratory studies have shown that treatment with hormones increases tumor cell death and reduces tumor cell growth. Both cancer progression. Is important to avoid metastasis, “Chuffa said. “Ingoing clinical trials have evaluated the use of melatonin to treat cancer. Specific treatments for different subtypes of breast cancer already exist and respond well to alternative treatments based on melatonin. Some patients do not. “

In search of the target gene

To identify molecular markers that guide cancer treatment, researchers first conducted meta-analysis-based studies where melatonin was found in the breast, head and neck, liver, stomach, prostate, central nervous system, and colorectal. We investigated how to regulate microRNA expression. cancer.

A meta-analysis involves systematically reviewing the literature using statistical methods and integrating the results of published studies on the same subject. MicroRNAs are small RNA molecules that do not encode proteins, but perform regulatory functions within the genome, regulate gene expression, and thus regulate several cellular processes.

“In this first step, we found 14 very recent studies linking melatonin to altered microRNA expression. For 7 focused cancers, we found 46 microRNAs with altered expression.” Said Chuffa.

Researchers then used bioinformatics to identify pathways associated with the action of hormones on tumor cells and analyze based on the association between these microRNAs and their regulatory targets. The regulatory and molecular network was generated and analyzed in collaboration with researchers Robson Francisco Carvalho, Luis Antonio Justulin, and Sara Santironi.

“When cross-referencing information with The Cancer Genome Atlas [TCGA]We have identified the target genes for these 46 microRNAs with altered expression, which is a public database. “

As a result, they were able to understand how melatonin functions in several cellular signaling pathways. “These genes targeted by melatonin are involved in important biological processes in cancer, such as cell cycle regulation, cell death, cell migration and aging,” he explained. “Melatonin appears to have a stronger effect on breast, oral, and gastric cancers. Prostate and colonic rectal tumors, and glioblastoma showed few changes induced by the microRNAs involved. “

Because breast cancer was associated with most genes and microRNAs at this first stage of the study, researchers found that microRNAs related to data obtained by RNA-seq analysis of breast tumors in mice treated with melatonin. We compared the target genes.

RNA-seq uses next-generation sequencing technology to study the expression of multiple genes simultaneously to obtain the complete set of RNA molecules expressed in the entire transcriptome, or tissue.

These analyzes were performed in collaboration with FAMERP researchers Débora Aparecida Pires de Campos Zuccari and Bruna Victorasso Jardim-Perassi.

“In animals treated with 40 milligrams of melatonin, signaling pathways associated with the immune system and apoptosis were enriched, reducing pathways associated with tumor aggression and metastasis,” Chuffa said.

The group also investigated specific proteins (transcription factors and kinases) that are active in processes such as transcription and the cell cycle. “The goal of this part of the study was to find a common target in cellular processes and public databases of breast cancer,” he said.

According to Chuffa, genes regulated by melatonin in breast cancer are potential targets for the treatment of this disease. “Because melatonin is a multitasking molecule that acts on a variety of cytosols, to investigate how hormones affect the expression of microRNAs and thus the regulation of identified cellular mechanisms. We are currently working on it, “he said.

Worms reveal why melatonin promotes sleep

For more information:

Luiz Gustavo de Almeida Chuffa et al, a meta-analysis of microRNA networks regulated by melatonin in cancer: portraits of potential candidates for breast cancer treatment, Pineal Gland Research Journal (2020). DOI: 10.1111 / jpi.12693

Quote: The study was obtained from on December 8, 2020 for treatment of breast cancer (December 8, 2020). Can direct the use of melatonin in

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Studies Can Direct the Use of Melatonin in the Treatment of Breast Cancer

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