TY - JOUR
T1 - 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
AU - Corrêa, Carolina Alves Pereira
AU - Andrade, Augusto Faria
AU - Veronez, Luciana Chain
AU - da Silva, Keteryne Rodrigues
AU - Baroni, Mirella
AU - Suazo, Veridiana Kill
AU - de Paula Gomes Queiroz, Rosane
AU - Lira, Régia Caroline Peixoto
AU - Chagas, Pablo Shimaoka
AU - Brandalise, Silvia Regina
AU - Yunes, José Andres
AU - Molina, Carlos Augusto Fernandes
AU - Antonini, Sonir Roberto Rauber
AU - Valera, Elvis Terci
AU - Tone, Luiz Gonzaga
AU - Scrideli, Carlos Alberto
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2024/12/1
Y1 - 2024/12/1
N2 - 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-β 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-β 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-β 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-β pathway changed. Together, the data indicate that both miRNAs participate in the TGF-β pathway and are therefore potential markers for predicting the prognosis of patients with pediatric ACT.
AB - 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-β 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-β 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-β 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-β pathway changed. Together, the data indicate that both miRNAs participate in the TGF-β pathway and are therefore potential markers for predicting the prognosis of patients with pediatric ACT.
KW - Adrenocortical tumor
KW - miRNA
KW - TGF-β
UR - http://www.scopus.com/inward/record.url?scp=85204209722&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2024.112371
DO - 10.1016/j.mce.2024.112371
M3 - Article
C2 - 39278396
AN - SCOPUS:85204209722
SN - 0303-7207
VL - 594
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
M1 - 112371
ER -