Institute of Biotechnology, Gebze Technical University, Gebze, 41400 Kocaeli, Turkey.
Department of Molecular Biology and Genetics, Atakoy Campus, Istanbul Kultur University, 34156 Istanbul, Turkey.
Int J Mol Sci. 2021 Feb 4;22(4):1557. doi: 10.3390/ijms22041557.
Breast cancer (BCa) is one of the leading health problems among women. Although significant achievements have led to advanced therapeutic success with targeted therapy options, more efforts are required for different subtypes of tumors and according to genomic, transcriptomic, and proteomic alterations. This study underlines the role of microRNA-21 (miR-21) in metastatic MDA-MB-231 breast cancer cells. Following the knockout of miR-21 from MDA-MB-231 cells, which have the highest miR-21 expression levels compared to MCF-7 and SK-BR-3 BCa cells, a decrease in epithelial-mesenchymal transition (EMT) via downregulation of mesenchymal markers was observed. Wnt-11 was a critical target for miR-21, and the Wnt-11 related signaling axis was altered in the stable miR-21 knockout cells. miR-21 expression was associated with a significant increase in mesenchymal markers in MDA-MB-231 BCa cells. Furthermore, the release of extracellular vesicles (EVs) was significantly reduced in the miR-21 KO cells, alongside a significant reduction in relative miR-21 export in EV cargo, compared with control cells. We conclude that miR-21 is a leading factor involved in mesenchymal transition in MDA-MB-231 BCa. Future therapeutic strategies could focus on its role in the treatment of metastatic breast cancer.
乳腺癌（BCa）是女性健康的主要问题之一。尽管靶向治疗选择取得了重大进展，但不同肿瘤亚型仍需要更多努力，并根据基因组、转录组和蛋白质组的改变进行调整。本研究强调了 microRNA-21（miR-21）在转移性 MDA-MB-231 乳腺癌细胞中的作用。与 MCF-7 和 SK-BR-3 BCa 细胞相比，MDA-MB-231 细胞中 miR-21 表达水平最高，敲除 miR-21 后观察到上皮-间充质转化（EMT）通过下调间充质标志物而减少。Wnt-11 是 miR-21 的关键靶标，稳定敲除 miR-21 细胞中的 Wnt-11 相关信号轴发生改变。miR-21 表达与 MDA-MB-231 BCa 细胞中间充质标志物的显著增加相关。此外，与对照细胞相比，miR-21 KO 细胞中细胞外囊泡（EVs）的释放显著减少，EV 货物中相对 miR-21 输出也显著减少。我们得出结论，miR-21 是 MDA-MB-231 BCa 中参与间充质转化的主要因素。未来的治疗策略可以集中在其在治疗转移性乳腺癌中的作用上。
