Neferine induces apoptosis and inhibits metastasis in human endometrial cancer cells by down-regulating miR-1266–5p

This study emphasizes the significance of dual role of microRNAs (miRNAs) in the anti-cancer effects of neferine (Nef), a natural compound derived from lotus embryos, specifically in endometrial cancer (EC) Ishikawa cells. We previously established that Nef induces apoptosis in EC cells, but did not delve into the specific miRNAs. Through a combination of mRNA and miRNA omics analyses, we identified miR-1266–5p as a key regulatory factor in this process. Subsequent phenotypic assays were performed to assess various cellular behaviors, including proliferation, apoptosis, calcium ion levels, mitochondrial membrane potential (MMP), and migration ability. Our findings demonstrate that down-regulation of miR-1266–5p could inhibit cell viability, induce cell apoptosis, increase intracellular Ca 2+ levels, decrease MMP, and suppress cell metastasis. Furthermore, the Ras/ERK and PI3K-AKT signaling pathways were identified as key mediators of miR-1266–5p on apoptosis and metastasis in Ishikawa cells. Overall, our study positions miR-1266–5p as a potential molecular marker for the diagnosis and prognosis of EC, as well as a promising candidate for therapeutic intervention. • The key factor miR-1266–5p has been screened out by combined mRNA-miRNA omics. •Downregulation of miR-1266–5p promotes Ishikawa cell apoptosis and inhibits cell migration. •PI3K-AKT, Ras/ERK signaling pathway was shown to be the key pathway. •MiR-1266–5p inhibitor acts as a tumor suppressor in Nef against endometrial cancer.