Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, 14115-111, Iran.
Sci Rep. 2024 Feb 27;14(1):4715. doi: 10.1038/s41598-024-52940-5.
MicroRNA expression in breast cancer (BC) is explored both as a potential biomarker and for therapeutic purposes. Recent studies have revealed that miR-203a-3p is involved in BC, and importantly contributes to BC chemotherapy responses; however, the regulatory pathways of miR-203a in BC remain elusive. Hence, we aimed to investigate the miR-203a regulatory mechanisms and their potential functions in the progress of BC. To this end, the miR-203a potential involving pathways was predicted by databases analyzing its target genes. The relations between miR-203a, the phosphatidylinositol 3'-kinase (PI3K)-Akt, and Wnt signaling pathways were mechanistically investigated. Our results revealed that miR-203a inhibited the activation of the PI3K/Akt and Wnt pathways and reduced its downstream cell cycle signals, including Cyclin D1 and c-Myc. Moreover, the overexpression of miR-203a drastically arrested the cell cycle at subG1 and G1 phases, decreased the viability, proliferation, and migration, and increased apoptosis of BC cells. Therefore, miR-203a-3p may be considered a tumor suppressor factor and a potential biomarker or therapeutic target for BC.
microRNA 在乳腺癌(BC)中的表达被探索为一种潜在的生物标志物和治疗目的。最近的研究表明,miR-203a-3p 参与了 BC,并对 BC 的化疗反应有重要贡献;然而,miR-203a 在 BC 中的调节途径仍不清楚。因此,我们旨在研究 miR-203a 的调节机制及其在 BC 进展中的潜在功能。为此,通过数据库分析其靶基因预测了 miR-203a 潜在涉及的途径。从机制上研究了 miR-203a 与磷脂酰肌醇 3'-激酶(PI3K)-Akt 和 Wnt 信号通路之间的关系。我们的结果表明,miR-203a 抑制了 PI3K/Akt 和 Wnt 通路的激活,并减少了其下游细胞周期信号,包括 Cyclin D1 和 c-Myc。此外,miR-203a 的过表达使 BC 细胞的细胞周期在 subG1 和 G1 期急剧停滞,降低了细胞活力、增殖和迁移,并增加了细胞凋亡。因此,miR-203a-3p 可被视为一种肿瘤抑制因子,也是 BC 的潜在生物标志物或治疗靶点。