M. Sc. Program in Biochemical Science, National Autonomous University of Mexico, 04510 Mexico City, Mexico.
Research Unit in Virology and Cancer, Children's Hospital of Mexico Federico Gómez, 06720 Mexico City, Mexico.
Int J Mol Sci. 2020 Oct 19;21(20):7720. doi: 10.3390/ijms21207720.
Breast cancer (BRCA) is a leading cause of mortality among women. Tumors often acquire aggressive features through genomic aberrations affecting cellular programs, e.g., the epithelial to mesenchymal transition (EMT). EMT facilitates metastasis leading to poor prognosis. We previously observed a correlation between an amplification of miR-650 (Amp-650) and EMT features in BRCA samples isolated from Mexican patients. In this study, we explored the cBioportal database aiming to extend that observation and better understand the importance of Amp-650 for BRCA aggressiveness. We found that Amp-650 is more frequent in aggressive molecular subtypes of BRCA, as well as in high grade poorly differentiated tumors, which we confirmed in an external miRNA expression database. We performed differential expression analysis on samples harboring Amp-650, taking advantage of gene target prediction tools and tumor suppressor gene databases to mine several hundreds of differentially underexpressed genes. We observed STAT5A as a likely putative target gene for miR-650 in aggressive poorly differentiated BRCA. Samples with both Amp-650 and low expression of STAT5A had less overall survival than samples with either or none of the alterations. No target gene has been described for miR-650 in BRCA, thus, this bioinformatic study provides valuable information that should be corroborated experimentally.
乳腺癌（BRCA）是女性死亡的主要原因之一。肿瘤经常通过影响细胞程序的基因组异常获得侵袭性特征，例如上皮到间充质转化（EMT）。EMT 促进转移，导致预后不良。我们之前观察到在从墨西哥患者中分离的 BRCA 样本中，miR-650 的扩增（Amp-650）与 EMT 特征之间存在相关性。在这项研究中，我们探索了 cBioportal 数据库，旨在扩展该观察结果，并更好地理解 Amp-650 对 BRCA 侵袭性的重要性。我们发现 Amp-650 在 BRCA 的侵袭性分子亚型中更为常见，以及在高级低分化肿瘤中更为常见，我们在外部 miRNA 表达数据库中证实了这一点。我们对携带 Amp-650 的样本进行了差异表达分析，利用基因靶标预测工具和肿瘤抑制基因数据库挖掘了数百个差异表达下调的基因。我们观察到 STAT5A 可能是 BRCA 中侵袭性低分化 miR-650 的一个潜在靶基因。与具有 Amp-650 和低表达 STAT5A 的样本相比，具有任一或均无这些改变的样本的总生存期更短。BRCA 中尚未描述 miR-650 的靶基因，因此，这项生物信息学研究提供了有价值的信息，应通过实验加以证实。
