Lycorine from Lycoris radiata induces M phase arrest in breast cancer by targeting miR-203a-3p-mediated MAPK signaling pathway

Objective To explore safe and effective precision management strategies for breast cancer based on Chinese herbal medicine, and to provide evidence for individualized therapy. Methods Lycorine, an alkaloid from Lycoris radiata , was investigated for its anti-breast cancer effects in Michigan cancer foundation (MCF)-7 cells. miRNA high-throughput sequencing was performed to identify differentially expressed miRNAs after lycorine treatment, followed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses to determine key regulatory pathways. The expression of miR-203a-3p and mitogen‑activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway-related proteins was examined by real-time quantitative PCR (qPCR) and Western blotting. Cell proliferation and cell cycle distribution were assessed using cell counting kit-8 (CCK-8) assay and flow cytometry. A dual-luciferase reporter assay was conducted to confirm the targeting relationship between miR-203a-3p and Kirsten rat sarcoma viral oncogene homolog (KRAS). Results The miRNA sequencing demonstrated that lycorine dose-dependently downregulated miR-203a-3p in MCF-7 cells. GO and KEGG analyses identified the MAPK/ERK signaling pathway as the principal pathway involved in lycorine-mediated inhibition of cell proliferation. qPCR and Western blotting confirmed that lycorine reduced the expression of miR-203a-3p and suppressed key components of the MAPK/ERK pathway at both mRNA and protein levels, including KRAS, v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), mitogen-activated protein kinase kinase 1/2 (MEK1/2), ERK1/2, as well as phosphorylated rapidly accelerated fibrosarcoma (p-RAF), p-MEK1/2, and p-ERK1/2. Functional assays showed that lycorine treatment or miR-203a-3p inhibition significantly suppressed MCF-7 cell proliferation and induced M−phase cell cycle arrest, whereas miR-203a-3p overexpression reversed these inhibitory effects. Dual-luciferase reporter assay verified that miR-203a-3p directly targeted KRAS. Hierarchical clustering further demonstrated coordinated regulation of MAPK/ERK pathway-related genes and proteins by lycorine, with high-dose lycorine producing effects comparable to direct miR-203a-3p inhibition. Conclusions The findings imply that miR-203a-3p has potential as a therapeutic target for the treatment of breast cancer. Furthermore, lycorine exerts its anti-tumor effects by modulating the miR-203a-3p/MAPK signaling axis, thereby providing a promising strategy for precision medicine in breast cancer treatment.