Análise transcriptômica de marcadores cronobiológicos e de células de Schwann associados a progressão do melanoma

Abstract

Melanoma is considered one of the most aggressive neoplastic types because it presents a rapid progression to metastasis, although several environmental and genetic factors have already been described that may influence the development and aggravate this tumor type, the deregulation in the circadian timing system remaining unattractive. Melatonin is the main hormone controlling the genes of the biological clock, it is known that an eventual change in the regulation of these genes can contribute to the development of several diseases including cancer. In this study, bioinformatics analyzes were performed with tissue data from melanoma and nonmelanoma skin cancer in order to assess which genes related to the biological clock may contribute to the progression of this tumor type. In addition, cell culture assays were carried out using melatonin as a treatment in non-melanoma cutaneous carcinoma cell lines (A431) and melanoma-type (B16) observing changes in these neoplastic cells. Changes in gene expression associated with clock, anticipation, migration, invasion and cell apoptosis genes in A432 and B16 cells after melatonin treatment were evaluated. In summary, genes related to the biological clock showed altered expression in melanoma skin cancer and these genes were associated with poor survival, according to the bioinformatics analysis. In cell culture, melatonin administration increased the expression of the PER2, CRY1 and CRY2 genes and experienced CLOCK gene expression levels. The PER2, CRY1 and CRY2 genes are considered tumor suppressor genes that can control events of importance in the tumor context, such as cell anticipation, apoptosis and control of the DNA repair and damage system. Melatonin administration has been shown to be able to induce behavioral changes in melanoma cells and influence the expression of genes MKI67, HIF-1A, VEGFA, COL1A1, CDH1, CASP3, BAX, BCL2, MMP9, PER2, CRY1, CRY2 AND CLOCK. The main cause of mortality from melanoma is metastatic dissemination and subsequent complications, despite advances in surgery and other methods of treatment, the survival rate of a patient with metastatic melanoma remains unchanged, only 4 years, in view of the data reported here, it is expected to contribute to therapeutic research by guiding the treatment of individuals who have this condition.