Analysis of miR-483-3p and miR-630 expression profile in pediatric adrenocortical tumors and the effect of their modulation on adrenal tumorigenesis in vitro

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Correa, Carolina Alves Pereira ; Andrade, Augusto Faria ; Veronez, Luciana Chain ; da Silva, Keteryne Rodrigues ; Baroni, Mirella ; Suazo, Veridiana Kill ; Queiroz, Rosane de Paula Gomes ; Lira, Regia Caroline Peixoto ; Chagas, Pablo Shimaoka ; Brandalise, Silvia Regina ; Yunes, Jose Andres ; Molina, Carlos Augusto Fernandes ; Antonini, Sonir Roberto Rauber ; Valera, Elvis Terci ; Tone, Luiz Gonzaga ; Scrideli, Carlos Alberto

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Cellular Endocrinology; v. 594, p. 11-pg., 2024-09-19.

Resumo

Pediatric adrenocortical tumors (ACT) are rare aggressive neoplasms with heterogeneous prognosis. MicroRNA (miRNA) signatures have been associated with cancer diagnosis, treatment response, and outcomes of several types of cancer. However, the role played by miRNAs in pediatric ACT has been poorly explored. In this study, we have evaluated the expression of miR-483-3p and miR-630 in 67 pediatric ACT and 19 non-neoplastic adrenal samples, the effects of the modulations of these miRNAs, and their relationship with the TGF-beta pathway in the H295R and H295A cell lines. Deregulation of both miRNAs was related to survival and disease advanced stages and hence to patients' prognosis. Moreover, modified miR-483-3p and miR-630 in vitro expression decreased cell viability and colony formation capacity, changed how some genes of the TGF-beta pathway, such as TGFBR1, TGFBR2, and SMAD7, are expressed, and altered Smad3, pSmad3, Smad 2/3, N-cadherin, and Vimentin protein expression. Besides that, when inhibition of the TGF-beta pathway was combined with miR-630 overexpression or miR-483-3p silencing, cell viability and colony formation capacity decreased, and protein expression in the TGF-beta pathway changed. Together, the data indicate that both miRNAs participate in the TGF-beta pathway and are therefore potential markers for predicting the prognosis of patients with pediatric ACT. (AU)

• Processo FAPESP: 10/07020-9 - Estudos moleculares em neoplasias da criança e do adolescente: assinatura de microRNAs e estudos funcionais de genes candidatos a terapia alvo
• Beneficiário: Carlos Alberto Scrideli
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/20341-0 - Interação entre alvos terapêuticos emergentes e vias de desenvolvimento associadas à tumorigênese: ênfase em neoplasias da criança e do adolescente
• Beneficiário: Luiz Gonzaga Tone
• Modalidade de apoio: Auxílio à Pesquisa - Temático