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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Gene co-expression and histone modification signatures are associated with melanoma progression, epithelial-to-mesenchymal transition, and metastasis

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Azevedo, Hatylas [1] ; Pessoa, Guilherme Cavalcante [2] ; de Luna Vitorino, Francisca Nathalia [3] ; Nsengimana, Jeremie [4, 5] ; Newton-Bishop, Julia [4] ; Reis, Eduardo Moraes [6] ; da Cunha, Julia Pinheiro Chagas [3] ; Jasiulionis, Miriam Galvonas [2]
Total Authors: 8
[1] Univ Fed Sao Paulo UNIFESP, Div Urol, Dept Surg, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo UNIFESP, Dept Pharmacol, Rua Pedro Toledo 669 5 Andar, BR-04039032 Sao Paulo, SP - Brazil
[3] Inst Butantan, Ctr Toxins Immune Response & Cell Signaling CeTIC, Lab Ciclo Celular, Sao Paulo - Brazil
[4] Univ Leeds, Inst Med Res St Jamess, Sch Med, Leeds, W Yorkshire - England
[5] Newcastle Univ, Populat Hlth Sci Inst, Biostat Res Grp, Newcastle - England
[6] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo - Brazil
Total Affiliations: 6
Document type: Journal article
Source: CLINICAL EPIGENETICS; v. 12, n. 1 AUG 24 2020.
Web of Science Citations: 0

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 type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 18/20775-0 - Non-coding RNAs involved with melanoma genesis and progression
Grantee:Miriam Galvonas Jasiulionis
Support type: 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 type: 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 type: Scholarships in Brazil - Scientific Initiation
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 type: Research Grants - Young Investigators Grants - Phase 2