School of Pharmacy, Nantong University, Nantong, Jiangsu 226019, China; Department of Pharmacy, Zhangjiagang Aoyang Hospital, Zhangjiagang, Jiangsu 215600, China.
School of Pharmacy, Nantong University, Nantong, Jiangsu 226019, China.
Biochem Pharmacol. 2024 Jul;225:116295. doi: 10.1016/j.bcp.2024.116295. Epub 2024 May 16.
Breast cancer (BC) is one of the most common malignant tumors in women. Angelica sinensis polysaccharide (ASP) is one of the main components extracted from the traditional Chinese medicine Angelica sinensis. Research has shown that ASP affects the progression of various cancers by regulating miRNA expression. This study aimed to explore the specific molecular mechanism by which ASP regulates BC progression through miR-3187-3p. After the overexpression or knockdown of miR-3187-3p and PDCH10 in BC cells, the proliferation, migration, invasion, and phenotype of BC cells were evaluated after ASP treatment. Bioinformatics software was used to predict the target genes of miR-3187-3p, and luciferase gene reporter experiments reconfirmed the targeted binding relationship. Subcutaneous tumor formation experiments were conducted in nude mice after the injection of BC cells. Western blot and Ki-67 immunostaining were performed on the tumor tissues. The results indicate that ASP can significantly inhibit the proliferation, migration, and invasion of BC cells. ASP can inhibit the expression of miR-3187-3p in BC cells and upregulate the expression of PDCH10 by inhibiting miR-3187-3p. A regulatory relationship exists between miR-3187-3p and PDCH10. ASP can inhibit the expression of β-catenin and phosphorylated glycogen synthase kinase-3β (p-GSK-3β) proteins through miR-3187-3p/PDCH10 and prevent the occurrence of malignant biological behavior in BC. Overall, this study revealed the potential mechanism by which ASP inhibits the BC process. ASP mediates the Wnt/β-catenin signaling pathway by affecting the miR-3187-3p/PDCH10 molecular axis, thereby inhibiting the proliferation, migration, invasion, and other malignant biological behaviors of BC cells.
乳腺癌（BC）是女性最常见的恶性肿瘤之一。当归多糖（ASP）是从中药当归中提取的主要成分之一。研究表明，ASP 通过调节 miRNA 的表达影响各种癌症的进展。本研究旨在通过 miR-3187-3p 探讨 ASP 调节 BC 进展的具体分子机制。在 BC 细胞中转染 miR-3187-3p 和 PDCH10 的过表达或敲低后，评估 ASP 处理后 BC 细胞的增殖、迁移、侵袭和表型。使用生物信息学软件预测 miR-3187-3p 的靶基因，并通过荧光素酶基因报告实验重新确认靶向结合关系。将 BC 细胞注射到裸鼠后进行皮下肿瘤形成实验。对肿瘤组织进行 Western blot 和 Ki-67 免疫染色。结果表明，ASP 可显著抑制 BC 细胞的增殖、迁移和侵袭。ASP 可抑制 BC 细胞中 miR-3187-3p 的表达，并通过抑制 miR-3187-3p 上调 PDCH10 的表达。miR-3187-3p 和 PDCH10 之间存在调节关系。ASP 可通过 miR-3187-3p/PDCH10 抑制 β-连环蛋白和磷酸化糖原合酶激酶-3β（p-GSK-3β）蛋白的表达，防止 BC 发生恶性生物学行为。综上所述，本研究揭示了 ASP 抑制 BC 进程的潜在机制。ASP 通过影响 miR-3187-3p/PDCH10 分子轴调节 Wnt/β-catenin 信号通路，从而抑制 BC 细胞的增殖、迁移、侵袭等恶性生物学行为。
