Integrating gene and microRNA expression, methylome and hidroxymethylome data from different phases of melanoma progression.

• Grant number: 14/13663-0
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2016
• End date: January 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Miriam Galvonas Jasiulionis
• Grantee: Miriam Galvonas Jasiulionis
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant(s): 17/50122-6 - Multiplex tissue analysis of the tumor microenvironment and crucial factors in melanoma pathogenesis, AP.R SPRINT

Abstract

Cutaneous melanomas are tumors extremely aggressive and poor responsive to therapies. Although several molecular alterations have already been described in melanomas, there is not an integrated knowledge of changes associated with different steps of melanoma genesis and progression. Knowing that both genetic and epigenetic alterations contribute to malignant transformation and tumor progression, we aimed to integrate data from transcriptome, methylome and hidroxymethylome analyses in a murine linear model composed by cell lines representing distinct phases of melanoma progression. The identified molecular alterations will be validated in human cell lines and samples from melanocytic lesions. The integrated analysis of these data may guide us to propose combined therapies to melanoma presenting specific characteristics. This study may contribute, not only with a better understanding of melanoma biology, but also to the identification of potential targets for therapy and biomarkers of prognostic and drug response. (AU)

Scientific publications

(13)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PESSOA, DIOGO DE OLIVEIRA; RIUS, FLAVIA EICHEMBERGER; ANGELO PAPAIZ, DEBORA D.; PEDROSO AYUB, ANA LUISA; MORAIS, ALICE SANTANA; DE SOUZA, CAMILA FERREIRA; DA PAIXAO, VINICIUS FERREIRA; SETUBAL, JOAO CARLOS; NEWTON-BISHOP, JULIA; NSENGIMANA, JEREMIE; et al. Transcriptional signatures underlying dynamic phenotypic switching and novel disease biomarkers in a linear cellular model of melanoma progression. Neoplasia, v. 23, n. 4, p. 439-455, APR 2021. (17/25321-5, 19/05641-0, 18/20775-0, 14/01168-5, 11/18959-7, 14/13663-0)

TORICELLI, MARIANA; MELO, FABIANA H. M.; HUNGER, ALINE; ZANATTA, DANIELA; STRAUSS, BRYAN E.; JASIULIONIS, MIRIAM G.. Timp1 Promotes Cell Survival by Activating the PDK1 Signaling Pathway in Melanoma. CANCERS, v. 9, n. 4, APR 2017. (10/18715-8, 14/13663-0, 11/12306-1)

DA CRUZ, ADRIANA TAVEIRA; HUNGER, ALINE; MACHADO DE MELO, FABIANA HENRIQUES; MONTEIRO, ANA CAROLINA; PARE, GENEVIEVE CATHERINE; LAI, DULCE; ALVES-FERNANDES, DEBORA KRISTINA; PEDROSO AYUB, ANA LUISA; CORDERO, ESTEBAN MAURICIO; DA SILVEIRA FILHO, JOSE FRANCO; et al. iR-138-5p induces aggressive traits by targeting Trp53 expression in murine melanoma cells, and correlates with poor prognosis of melanoma patient. Neoplasia, v. 23, n. 8, p. 823-834, AUG 2021. (12/08776-5, 18/20775-0, 10/18484-6, 14/13663-0)

MONTEIRO, ANA CAROLINA; MUENZNER, JULIENNE K.; ANDRADE, FERNANDO; RIUS, FLAVIA EICHEMBERGER; OSTALECKI, CHRISTIAN; GEPPERT, CAROL I.; AGAIMY, ABBAS; HARTMANN, ARNDT; FUJITA, ANDRE; SCHNEIDER-STOCK, REGINE; et al. Gene expression and promoter methylation of angiogenic and lymphangiogenic factors as prognostic markers in melanoma. MOLECULAR ONCOLOGY, v. 13, n. 6, p. 1433-1449, JUN 2019. (16/09179-1, 13/04829-0, 14/13663-0, 17/50122-6)

MACHADO DE MELO, FABIANA HENRIQUES; GONCALVES, DIEGO ASSIS; DE SOUSA, RICARDO XISTO; ICIMOTO, MARCELO YUDI; FERNANDES, DENISE DE CASTRO; LAURINDO, FRANCISCO R. M.; JASIULIONIS, MIRIAM GALVONAS. Metastatic Melanoma Progression Is Associated with Endothelial Nitric Oxide Synthase Uncoupling Induced by Loss of eNOS:BH4 Stoichiometry. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 17, SEP 2021. (14/13663-0, 17/10695-7, 17/04352-0)

PAPAIZ, DEBORA D'ANGELO; RIUS, FLAVIA EICHEMBERGER; AYUB, ANA LUISA PEDROSO; ORIGASSA, CLARICE S.; GUJAR, HEMANT; PESSOA, DIOGO DE OLIVEIRA; REIS, EDUARDO MORAES; NSENGIMANA, JEREMIE; NEWTON-BISHOP, JULIA; MASON, CHRISTOPHER E.; et al. Genes regulated by DNA methylation are involved in distinct phenotypes during melanoma progression and are prognostic factors for patients. MOLECULAR ONCOLOGY, v. 16, n. 9, p. 18-pg., 2022-02-04. (19/23480-4, 14/13663-0, 18/20775-0)

MELISO, FABIANA M.; MICALI, DANILO; SILVA, CAMILA T.; SABEDOT, THAIS S.; COETZEE, SIMON G.; KOCH, ADRIAN; FAHLBUSCH, FABIAN B.; NOUSHMEHR, HOUTAN; SCHNEIDER-STOCK, REGINE; JASIULIONIS, MIRIAM G.. SIRT1 regulates Mxd1 during malignant melanoma progression. ONCOTARGET, v. 8, n. 70, p. 114540-114553, DEC 29 2017. (16/06488-3, 15/07925-5, 11/12306-1, 14/13663-0)

PESSOA, DIOGO DE OLIVEIRA; RIUS, FLAVIA EICHEMBERGER; ANGELO PAPAIZ, DEBORA D.; PEDROSO AYUB, ANA LUISA; MORAIS, ALICE SANTANA; DE SOUZA, CAMILA FERREIRA; DA PAIXAO, VINICIUS FERREIRA; SETUBAL, JOAO CARLOS; NEWTON-BISHOP, JULIA; NSENGIMANA, JEREMIE; et al. Transcriptional signatures underlying dynamic phenotypic switching and novel disease biomarkers in a linear cellular model of melanoma progression. NEOPLASIA, v. 23, n. 4, p. 17-pg., 2021-04-09. (11/18959-7, 17/25321-5, 14/01168-5, 18/20775-0, 14/13663-0, 19/05641-0)

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. Gene co-expression and histone modification signatures are associated with melanoma progression, epithelial-to-mesenchymal transition, and metastasis. CLINICAL EPIGENETICS, v. 12, n. 1, p. 24-pg., 2020-08-24. (17/18344-9, 18/15553-9, 18/20775-0, 14/13663-0, 18/04254-0)

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. Gene co-expression and histone modification signatures are associated with melanoma progression, epithelial-to-mesenchymal transition, and metastasis. CLINICAL EPIGENETICS, v. 12, n. 1, AUG 24 2020. (17/18344-9, 18/20775-0, 14/13663-0, 18/04254-0, 18/15553-9)

GONCALVES, DIEGO ASSIS; XISTO, RICARDO; GONCALVES, JESSICA DOMINGUES; DA SILVA, DOUGLAS BACETI; MOURA SOARES, JAQUELINE PEREIRA; ICIMOTO, MARCELO YUDI; SANT'ANNA, CARLA; GIMENEZ, MARCELA; DE ANGELIS, RADA; LLESUY, SUSANA; et al. Imbalance between nitric oxide and superoxide anion induced by uncoupled nitric oxide synthase contributes to human melanoma development. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, v. 115, OCT 2019. (17/10695-7, 14/13663-0, 17/04352-0)

JASIULIONIS, MIRIAM G.. Abnormal Epigenetic Regulation of Immune System during Aging. FRONTIERS IN IMMUNOLOGY, v. 9, FEB 12 2018. (14/13663-0)

RIUS, FLAVIA E.; PAPAIZ, DEBORA D.; AZEVEDO, HATYLAS F. Z.; AYUB, ANA LUISA P.; PESSOA, DIOGO O.; OLIVEIRA, TIAGO F.; LOUREIRO, ANA PAULA M.; ANDRADE, FERNANDO; FUJITA, ANDRE; REIS, EDUARDO M.; et al. Genome-wide promoter methylation profiling in a cellular model of melanoma progression reveals markers of malignancy and metastasis that predict melanoma survival. CLINICAL EPIGENETICS, v. 14, n. 1, p. 20-pg., 2022-12-01. (19/23480-4, 18/20775-0, 14/13663-0)