Association of miR-181a-5p with Lantana camara leaf extract-mediated inhibition of proliferation, survival, and migration in luminal A-type MCF-7 cells and triple-negative type MDA-MB-231 cells

Abstract Ethnopharmacological relevance Breast cancer has a high mortality with increasing chemoresistance and recurrence. Lantana camara has diverse medicinal properties, including anti-cancer potential; however, its role in breast cancer is not well-explored. Aim of the study The study aims to elucidate the role of Lantana camara leaf extract in miR-181a-5p-mediated control of proliferation, survival, and migration of breast cancer cells. Material and methods Real-time PCR was employed for RNA expression studies. Bioinformatic tools were used for identifying miR-181a-5p target mRNAs and seed regions in the 3 prime untranslated region of target mRNAs. miR-181a-5p was overexpressed in cells using transfection method. Flow cytometry was employed for cell cycle and apoptosis assays. Scratch assay was performed to study cell migration. The 3 prime untranslated region of CDKN3 was cloned, and site-directed mutagenesis was employed to mutate miR-181a-5p seed region. Western blot analysis was employed for a reporter assay. Results L. camara leaf extract upregulated the expression of miR-181a-5p with concomitant decrease in mRNAs of BCL-2 , MCL-1 , and CDKN3 in breast cancer cells. Overexpression of miR-181a-5p induced cell death in MCF-7 and MDA-MB-231 cells, and cell death increased in the presence of leaf extract. miR-181a impeded migration in both cell lines in the presence of the extract. Reporter assay confirmed the interaction of miR-181a-5p with 3 prime untranslated region of the CDKN3 mRNA. Conclusion Our study suggests that the extract may play an important role in regulating miR-181a-5p in MCF-7 and MDA-MB-231 cells, and may have important therapeutic potential for breast cancer therapy.