The role of the miR-30a-5p/BCL2L11 pathway in rosmarinic acid-induced apoptosis in MDA-MB-231-derived breast cancer stem-like cells

作者：Wei Wang, Yuefen Zhang, Xiaomin Huang, Dan Li, Qi Lin, Hai-Lin Zhuang, Hong Li · 发表于：Frontiers in Pharmacology · 年份：2024 · DOI：10.3389/fphar.2024.1445034 · 被引用次数：6 · 研究领域：MicroRNA in disease regulation、Cancer, Lipids, and Metabolism、Plant-Derived Bioactive Compounds

Background Rosmarinic acid (RA), a natural phenolic acid, exhibits promising anti-cancer properties. The abnormal expression of microRNA (miRNA) regulates the gene expression and plays a role as an oncogenic or tumor suppressor in TNBC. However, the biological role of RA in miR-30a-5p on BCL2L11 during MDA-MB-231 induced breast cancer stem-like cells (BCSCs) progression and its regulatory mechanism have not been elucidated. Objective To investigate whether RA inhibited the silencing effect of miR-30a-5p on the BCL2L11 gene and promoted apoptosis in BCSCs. Materials and Methods We assessed the migration, colony formation, proliferation, cell cycle, and apoptosis of BCSCs after RA treatment using the wound-healing assay, colony formation assay, CCK-8 assay, and flow cytometry, respectively. The expression of mRNA and protein levels of BCL-2, Bax, BCL2L11, and P53 genes in BCSCs after RA treatment was obtained by real-time polymerase chain reaction and Western blot. Differential miRNA expression in BCSCs was analyzed by high-throughput sequencing. Targetscan was utilized to predict the targets of miR-30a-5p. The dual luciferase reporter system was used for validation of the miR-30a-5p target. Results Wound-healing assay, colony formation assay, CCK-8 assay, and cell cycle assay results showed that RA inhibited migration, colony formation and viability of BCSCs, and cell cycle arrest in the G0-G1 phase. At the highest dose of RA, we noticed cell atrophy, while the arrest rate at ...