Alves Michelle Teodoro, da Conceição Izabela Mamede Costa Andrade, de Oliveira Angélica Navarro, Oliveira Heloísa Helena Marques, Soares Cintia Esteves, de Paula Sabino Adriano, Silva Luciana Maria, Simões Ricardo, Luizon Marcelo Rizzatti, Gomes Karina Braga
Departamento de Análises Clínicas eToxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, CEP 31270-901, Brazil.
Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Cardiovasc Toxicol. 2022 Jul;22(7):655-662. doi: 10.1007/s12012-022-09748-4. Epub 2022 May 7.
Cardiovascular toxicity is the main adverse effect of Doxorubicin (DOX) in cancer patients. microRNAs (miRNAs) are promising biomarkers to identify cardiac injury induced by DOX in breast cancer patients during the subclinical phase. Using RT-qPCR, we compared the expression of circulating miR-208a5p, miR-133a, miR-499a5p, miR-15a, miR-133b, and miR-49a3p in serum samples from DOX-induced cardiotoxicity (case) compared to the non-cardiotoxicity group (control). To further explore the potential roles of these circulating miRNA in cardiotoxicity, we searched the miRTarBase for experimentally validated miRNA-target interactions and performed a functional enrichment analysis based on those interactions. miR-133a was significantly upregulated in case compared to control group. The most relevant pathway regulated by miR-133a was ErbB2 signaling, whose main genes involved are EGFR, ERBB2, and RHOA, which are possibly downregulated by miR133a. The other miRNAs did not show significant differential expression when compared on both groups. The data suggest that miR-133a is associated with DOX-based cardiotoxicity during chemotherapy in breast cancer patients through ErbB2 signaling pathway. Moreover, miR-133a may be a future marker of DOX-induced cardiotoxicity in women with breast cancer.
心血管毒性是阿霉素（DOX）在癌症患者中的主要不良反应。微小RNA（miRNA）是有前景的生物标志物，可用于在亚临床阶段识别乳腺癌患者中由DOX诱导的心脏损伤。我们使用逆转录定量聚合酶链反应（RT-qPCR），比较了阿霉素诱导的心脏毒性患者（病例组）与非心脏毒性组（对照组）血清样本中循环miR-208a-5p、miR-133a、miR-499a-5p、miR-15a、miR-133b和miR-49a-3p的表达。为了进一步探索这些循环miRNA在心脏毒性中的潜在作用，我们在miRTarBase中搜索了经过实验验证的miRNA-靶标相互作用，并基于这些相互作用进行了功能富集分析。与对照组相比，病例组中miR-133a显著上调。miR-133a调控的最相关通路是ErbB2信号通路，其主要涉及的基因有表皮生长因子受体（EGFR）、人表皮生长因子受体2（ERBB2）和RHOA，这些基因可能被miR-133a下调。在两组之间比较时，其他miRNA未显示出显著差异表达。数据表明，miR-133a在乳腺癌患者化疗期间通过ErbB2信号通路与基于阿霉素的心脏毒性相关。此外，miR-133a可能是乳腺癌女性中阿霉素诱导的心脏毒性的未来标志物。
