The role of lncRNAs and regulatory networks regarding lncRNAs, miRNAs e mRNAs in Melanoma progression

Abstract

It is estimated that around 90% of the genome is transcribed into non-coding RNA (ncRNA). The ncRNAs can be classified into small (such as the miRNAs) and long (lncRNA), and both, have been previously reported participating in biological processes such as proliferation, differentiation and cellular migration. Changes in their expression have been associated to several diseases, including Cancer. Furthermore, recent studies have showed that lncRNAs can regulate the epigenetic machinery through chromatin silencing and remodeling, and can also regulate and be regulated by miRNAs. Melanoma is one of the most aggressive types of Cancer, developing high probability of metastasis and showing an unfavorable response to therapies. Our lab has developed a model of Melanoma progression, in which different cell lines represent distinct stages of the progression model were established by exposing nontumorigenic melanocytes to sustained stressed conditions (cycles of adhesion blockage). The aim of this work is to identify lncRNAs that have specific roles in the Melanoma progression and understand their mechanisms of action, through integrative analyses of RNA-seq and microarrays data, searching for possible lncRNA pathways acting with mRNA and miRNAs during the Melanoma progression. Previous data comparing the RNA sequencing results of the 4 cell lines of our model (melan-a, nontumorigenic melanocytes; 4C, premalignant melanocytes; 4C11-, non-metastatic Melanoma cells; 4C11+, metastatic Melanoma cells), identified a total of 3032 genes, coding and non-coding, which displayed differentiated expression levels when comparing two or more cell lines, out of which 5 genes, being 1 protein coding and 4 lncRNAs, were selected for this project. The lncRNAs identified in this work will be assessed through functional assays in vitro and tumorigenicity assay in vivo. The results could be used as the foundation for new prognostics techniques, diagnostic and Melanoma therapy, at the same time as it may contribute to a better understanding of the role of lncRNAs on the Melanoma genesis and progression. (AU)