| Full text | |
| Author(s): |
Azevedo, Hatylas
;
Pessoa, Guilherme Cavalcante
;
de Luna Vitorino, Francisca Nathalia
;
Nsengimana, Jeremie
;
Newton-Bishop, Julia
;
Reis, Eduardo Moraes
;
da Cunha, Julia Pinheiro Chagas
;
Jasiulionis, Miriam Galvonas
Total Authors: 8
|
| Document type: | Journal article |
| Source: | CLINICAL EPIGENETICS; v. 12, n. 1, p. 24-pg., 2020-08-24. |
| Abstract | |
Background We have previously developed a murine cellular system that models the transformation from melanocytes to metastatic melanoma cells. This model was established by cycles of anchorage impediment of melanocytes and consists of four cell lines: differentiated melanocytes (melan-a), pre-malignant melanocytes (4C), malignant (4C11-), and metastasis-prone (4C11+) melanoma cells. Here, we searched for transcriptional and epigenetic signatures associated with melanoma progression and metastasis by performing a gene co-expression analysis of transcriptome data and a mass-spectrometry-based profiling of histone modifications in this model. Results Eighteen modules of co-expressed genes were identified, and some of them were associated with melanoma progression, epithelial-to-mesenchymal transition (EMT), and metastasis. The genes in these modules participate in biological processes like focal adhesion, cell migration, extracellular matrix organization, endocytosis, cell cycle, DNA repair, protein ubiquitination, and autophagy. Modules and hub signatures related to EMT and metastasis (turquoise, green yellow, and yellow) were significantly enriched in genes associated to patient survival in two independent melanoma cohorts (TCGA and Leeds), suggesting they could be sources of novel prognostic biomarkers. Clusters of histone modifications were also linked to melanoma progression, EMT, and metastasis. Reduced levels of H4K5ac and H4K8ac marks were seen in the pre-malignant and tumorigenic cell lines, whereas the methylation patterns of H3K4, H3K56, and H4K20 were related to EMT. Moreover, the metastatic 4C11+ cell line showed higher H3K9me2 and H3K36me3 methylation, lower H3K18me1, H3K23me1, H3K79me2, and H3K36me2 marks and, in agreement, downregulation of the H3K36me2 methyltransferase Nsd1. Conclusions We uncovered transcriptional and histone modification signatures that may be molecular events driving melanoma progression and metastasis, which can aid in the identification of novel prognostic genes and drug targets for treating the disease. (AU) | |
| FAPESP's process: | 17/18344-9 - Quantitative chromatin proteomics upon FGF2 treatment: analysis of transcriptional regulation and involvement of cdc42 |
| Grantee: | Francisca Nathália de Luna Vitorino |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 18/15553-9 - Going deeper into Trypanosoma cruzi chromatin regulation: identifying new players and quizzing its impact on a potential transcription control |
| Grantee: | Julia Pinheiro Chagas da Cunha |
| Support Opportunities: | Research Grants - Young Investigators Grants - Phase 2 |
| FAPESP's process: | 18/20775-0 - Non-coding RNAs involved with melanoma genesis and progression |
| Grantee: | Miriam Galvonas Jasiulionis |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 14/13663-0 - Integrating gene and microRNA expression, methylome and hidroxymethylome data from different phases of melanoma progression. |
| Grantee: | Miriam Galvonas Jasiulionis |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 18/04254-0 - Global profile of histone marks at distinct stages of melanoma progression and its impact on malignancy characteristics |
| Grantee: | Guilherme Cavalcante Pessoa |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |