Bhattarai Shristi, Sugita Bruna M, Nunes-Souza Emanuelle, Fonseca Aline S, Chandrashekar Darshan Shimoga, Bhargava Mahak, Cavalli Luciane R, Aneja Ritu
Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, GA 30144, USA.
Department of Biology, Georgia State University, Atlanta, GA 30302, USA.
Int J Mol Sci. 2024 Dec 21;25(24):13679. doi: 10.3390/ijms252413679.
Androgen receptor (AR)-negative triple-negative breast cancer (TNBC), often termed quadruple-negative breast cancer (QNBC), disproportionately impacts women of African descent, leading to poorer overall survival (OS). MiRNAs regulate the expression of gene drivers involved in critical signaling pathways in TNBC, such as the gene, and their expression varies across races and breast cancer subtypes. This study investigates whether differentially expressed miRNAs influence AR transcription, potentially contributing to the observed disparities between African American (AA) and European American (EA) QNBC patients. Race-annotated TNBC samples (n = 129) were analyzed for AR expression status and revealed the prevalence of QNBC in AA patients compared to EA (76.6% vs. 57.7%) and a significant association of AR loss with poor survival among AAs. The Cancer Genome Atlas (TCGA) RNA-seq data showed that AAs with TNBC (n = 32) had lower AR mRNA levels than EAs (n = 67). Among TCGA patients in the AR-low group, AAs had significantly poorer OS than EAs. In our cohort, 46 miRNAs exhibited differential expression between AAs and EAs with QNBC. Ten of these miRNAs (miR-1185-5p, miR-1305, miR-3161, miR-3690, miR-494-3p, miR-509-3-5p, miR-619-3p, miR-628-3p, miR-873-5p, and miR-877-5p) were predicted to target the AR gene/signaling. The loss of AR expression is linked to poorer prognoses in AA women. The understanding of the specific miRNAs involved and their regulatory mechanisms on AR expression could provide valuable insights into why AA women are more prone to QNBC.
雄激素受体（AR）阴性的三阴性乳腺癌（TNBC），常被称为四阴性乳腺癌（QNBC），对非洲裔女性的影响尤为严重，导致总体生存率（OS）更低。微小RNA（miRNA）可调节TNBC关键信号通路中涉及的基因驱动因子的表达，比如 基因，并且它们的表达在不同种族和乳腺癌亚型之间存在差异。本研究调查了差异表达的miRNA是否会影响AR转录，这可能导致非裔美国（AA）和欧美（EA）QNBC患者之间出现所观察到的差异。对带有种族注释的TNBC样本（n = 129）进行AR表达状态分析，结果显示与EA患者相比，AA患者中QNBC的患病率更高（76.6%对57.7%），并且AR缺失与AA患者的不良生存显著相关。癌症基因组图谱（TCGA）的RNA测序数据表明，患有TNBC的AA患者（n = 32）的AR mRNA水平低于EA患者（n = 67）。在AR低表达组的TCGA患者中，AA患者的OS明显比EA患者差。在我们的队列中，46种miRNA在患有QNBC的AA和EA患者之间表现出差异表达。其中10种miRNA（miR-1185-5p、miR-1305、miR-3161、miR-3690、miR-494-3p、miR-509-3-5p、miR-619-3p、miR-628-3p、miR-873-5p和miR-877-5p）被预测靶向AR基因/信号通路。AR表达缺失与AA女性较差的预后相关。了解所涉及的特定miRNA及其对AR表达的调控机制，可为AA女性更易患QNBC的原因提供有价值的见解。
