Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, HCFMUSP, São Paulo, SP, Brazil.
Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, HCFMUSP, São Paulo, SP, Brazil; Setor de Mastologia, Disciplina de Ginecologia, Universidade de Brasília, Brasília, DF, Brazil.
Clinics (Sao Paulo). 2023 Jan 19;78:100155. doi: 10.1016/j.clinsp.2022.100155. eCollection 2023.
FOXO3a dysregulation is frequently implicated in tumorigenesis, and its inhibition can occur by several molecular mechanisms. Among these, post-transcriptional suppression by miRNAs has been associated with various cancers initiation. Here, we assessed the expression profiles of the most relevant miRNAs for breast tumorigenesis, using Luminal A (LA) and Triple-Negative (TN) breast cancer from Brazilian patients, by the quantitative real time-PCR method. Their potential prognostic role for the patients was also evaluated. We identified the miRNAs miR-96-5p and miR-182-5p, de-scribed as negative regulators of FOXO3A, with differential expression both in LA and TN tumors when compared to normal tissue. The miR-96-5p and miR-182-5p miRNAs were upregulated in LA (7.82 times, p < 0.005; 6.12 times, p < 0.005, respectively) and TN breast cancer samples (9.42 times, p < 0.0001; 8.51 times, p < 0.0001) compared to normal tissues. The samples with higher miR-96-5p and miR-182-5p expression (FR ≥ 4) were submitted for FOXO3a immunostaining. Reduced protein detection was observed in all of the tumors compared to normal tissues. The most prominent miRNA expression and FOXO3a protein suppression were observed in TN samples (p < 0.001), indicating the relevant role of these molecules in this tumor biology and clinical behavior. Our results corroborate the literature regarding to the relevance of FOXO3a in the breast cancer, and they open new perspectives for alternative target therapy options for Brazilian patients expressing both FOXO3a and its regulatory miRNAs.
FOXO3a 失调经常与肿瘤发生有关，其抑制可以通过几种分子机制发生。在这些机制中，miRNAs 的转录后抑制与各种癌症的发生有关。在这里，我们使用巴西患者的 Luminal A (LA) 和三阴性 (TN) 乳腺癌，通过定量实时 PCR 方法评估了与乳腺癌发生最相关的 miRNAs 的表达谱。还评估了它们对患者的潜在预后作用。我们确定了 miRNA miR-96-5p 和 miR-182-5p，它们被描述为 FOXO3A 的负调节剂，在与正常组织相比时，在 LA 和 TN 肿瘤中均有差异表达。miR-96-5p 和 miR-182-5p 在 LA（分别为 7.82 倍，p<0.005；6.12 倍，p<0.005）和 TN 乳腺癌样本（9.42 倍，p<0.0001；8.51 倍，p<0.0001）中上调与正常组织相比。miR-96-5p 和 miR-182-5p 表达（FR≥4）较高的样本进行了 FOXO3a 免疫染色。与正常组织相比，所有肿瘤中均观察到蛋白检测减少。在 TN 样本中观察到最明显的 miRNA 表达和 FOXO3a 蛋白抑制（p<0.001），表明这些分子在这种肿瘤生物学和临床行为中的重要作用。我们的结果与文献中关于 FOXO3a 在乳腺癌中的相关性一致，并为巴西表达 FOXO3a 及其调节 miRNA 的患者提供了新的靶向治疗选择的前景。
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