Molecular studies in neoplasias of children and adolescents: microRNAs signature and functional studies of candidate genes to target therapy

• Grant number: 10/07020-9
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2011
• End date: March 31, 2014
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Carlos Alberto Scrideli
• Grantee: Carlos Alberto Scrideli
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Carlos Eduardo Martinelli Junior ; Carlos Gilberto Carlotti Jr ; Elvis Terci Valera ; Helio Rubens Machado ; José Andrés Yunes ; Luciano Neder Serafini ; Luiz Gonzaga Tone ; Margaret de Castro ; Ricardo Santos de Oliveira ; Rodrigo Alexandre Panepucci ; Rosane Gomes de Paula Queiroz ; Silvia Regina Brandalise ; Silvio Tucci Junior ; Sonir Roberto Rauber Antonini

Abstract

Differences in the microRNA (miRs) signature and functional studies of genes associated to cancer could help in diagnosis, prognosis and suggest new insights in important pathways that could be used as potential therapeutic targets in human malignancies. The aim of this project is to identify miR signatures in different pediatric tumors (acute lymphoblastic leukemia, central nervous system tumors and adrenocortical tumors) and to evaluate the differential miR profile in specific subgroups of these malignancies and also to study the function of genes identified in previous group studies, with potential to be used as therapeutic target in new therapeutic protocol design, especially in poor prognosis patients. Functional studies will be made by silencing and/or activation of selected genes by assays of citotoxicity, cell viability and proliferation, apoptosis and cycle cell, and will include the genes SHOC2 and XPO7 in acute lymphoblastic leukemia cell lines, TNFA and AURKB in adrenocortical tumor cell lines, and VEGF and CA12 in astrocytic tumors and medulloblastoma cell lines. Until now the tumor bank of the participant institutions had stored more than 200 acute lymphoblastic leukemia samples, 60 of children adrenocortical tumors, 15 adult adrenocortical tumors, 50 meddulloblastomas, 50 pilocyticc astrocytomas, 50 glioblastomas as well as non-neoplastic control samples (bone marrow, adrenal and brain tissues). (AU)

Scientific publications

(9)

(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)

BORGES, KLEITON S.; ANDRADE, AUGUSTO F.; SILVEIRA, VANESSA S.; MARCO ANTONIO, DAVID S.; VASCONCELOS, ELTON J. R.; ANTONINI, SONIR R. R.; TONE, LUIZ G.; SCRIDELI, CARLOS A.. The aurora kinase inhibitor AMG 900 increases apoptosis and induces chemosensitivity to anticancer drugs in the NCI-H295 adrenocortical carcinoma cell line. ANTI-CANCER DRUGS, v. 28, n. 6, p. 634-644, JUL 2017. (10/07020-9, 10/08699-5)

DARRIGO JUNIOR, LUIZ GUILHERME; PEIXOTO LIRA, REGIA CAROLINE; FEDATTO, PAOLA FERNANDA; MARCO ANTONIO, DAVID SANTOS; VALERA, ELVIS TERCI; AGUIAR, SIMONE; YUNES, JOSE ANDRES; BRANDALISE, SILVIA REGINA; NEDER, LUCIANO; SAGGIORO, FABIANO PINTO; et al. MicroRNA profile of pediatric pilocytic astrocytomas identifies two tumor-specific signatures when compared to non-neoplastic white matter. JOURNAL OF NEURO-ONCOLOGY, v. 141, n. 2, p. 373-382, JAN 2019. (10/07020-9)

PEIXOTO LIRA, REGIA CAROLINE; FEDATTO, PAOLA FERNANDA; MARCO ANTONIO, DAVID SANTOS; LEAL, LETICIA FERRO; MARTINELLI, CARLOS EDUARDO; DE CASTRO, MARGARET; TUCCI, SILVIO; NEDER, LUCIANO; RAMALHO, LEANDRA; SEIDINGER, ANA LUIZA; et al. IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis. Endocrine-Related Cancer, v. 23, n. 6, p. 481-493, JUN 2016. (10/07020-9)

DA SILVA, KETERYNE RODRIGUES; VERONEZ, LUCIANA CHAIN; PEREIRA CORREA, CAROLINA ALVES; PEIXOTO LIRA, REGIA CAROLINE; BARONI, MIRELLA; SILVA QUEIROZ, ROSANE DE PAULA; RAUBER ANTONINI, SONIR ROBERTO; YUNES, JOSE ANDRES; BRANDALISE, SILVIA REGINA; TONE, LUIZ GONZAGA; et al. MicroRNA-149-3p expression correlates with outcomes of adrenocortical tumor patients and affects proliferation and cell cycle progression of H295A adrenocortical cancer cell line. HUMAN CELL, v. 35, n. 6, p. 9-pg., 2022-09-02. (10/07020-9, 14/20341-0)

DARRIGO JUNIOR, LUIZ GUILHERME; BARONI, MIRELLA; PEIXOTO LIRA, REGIA CAROLINE; TEIXEIRA, SILVIA; FEDATTO, PAOLA FERNANDA; SILVEIRA, VANESSA SILVA; SUAZO, VERIDIANA KILL; VERONEZ, LUCIANA CHAIN; PANEPUCCI, RODRIGO ALEXANDRE; MARCO ANTONIO, DAVID SANTOS; et al. High-throughput microRNA profile in adult and pediatric primary glioblastomas: the role of miR-10b-5p and miR-630 in the tumor aggressiveness. MOLECULAR BIOLOGY REPORTS, v. 47, n. 9, SEP 2020. (10/07020-9)

VERONEZ, L.; ALVES, C.; FEDATTO, P.; LIRA, R. C.; BARONI, M.; SILVA, K.; SANTOS, P.; ANTONIO, D. S.; QUEIROZ, R.; ANTONINI, S.; et al. Microrna Expression Profile Identifies Subgroups of Pediatric Adrenocortical Tumors with Different Clinical Outcomes. PEDIATRIC BLOOD & CANCER, v. 68, p. 2-pg., 2021-11-01. (10/07020-9, 14/20341-0)

LUCON, DANIELLE RIBEIRO; ROCHA, CRISTIANE DE SOUZA; CRAVEIRO, ROGERIO BASTOS; DILLOO, DAGMAR; CARDINALLI, LZILDA A.; CAVALCANTI, DENISE PONTES; AGUIAR, SIMONE DOS SANTOS; MAURER-MORELLI, CLAUDIA; YUNES, JOSE ANDRES. Downregulation of 14q32 microRNAs in primary human desmoplastic medulloblastoma. FRONTIERS IN ONCOLOGY, v. 3, p. 14-pg., 2013-01-01. (10/07020-9)

VERONEZ, LUCIANA CHAIN; FEDATTO, PAOLA FERNANDA; CORREA, CAROLINA ALVES PEREIRA; LIRA, REGIA CAROLINE PEIXOTO; BARONI, MIRELLA; DA SILVA, KETERYNE RODRIGUES; SANTOS, PAULA; ANTONIO, DAVID SANTOS MARCO; QUEIROZ, ROSANE DE PAULA SILVA; ANTONINI, SONIR ROBERTO RAUBER; et al. MicroRNA expression profile predicts prognosis of pediatric adrenocortical tumors. PEDIATRIC BLOOD & CANCER, DEC 2021. (10/07020-9, 14/20341-0)

SILVEIRA, VANESSA S.; FREIRE, BRUNO M. R.; BORGES, KLEITON S.; ANDRADE, AUGUSTO F.; CRUZEIRO, GUSTAVO A. V.; SABINO, JOAO PAULO J.; GLASS, MOGENS LESNER; YUNES, JOSE ANDRES; BRANDALISE, SILVIA REGINA; TONE, LUIZ GONZAGA; et al. Hypoxia-related gene expression profile in childhood acute lymphoblastic leukemia: prognostic implications. Leukemia & Lymphoma, v. 55, n. 8, p. 1751-1757, AUG 2014. (10/06067-1, 10/07020-9)