Breast cancer is one of the most prevalent malignancies among women worldwide. There is no targeted therapy currently available for the treatment of patients with triple negative breast cancer (TNBC). Metastasis is the primary cause of death in cancer patients. Gelatinase B (MMP-9) plays a central role in invasion and metastasis of breast cancer cells. Here we show that, in triple negative MDA-MB-231 breast cancer cell line, hsa-mir-491 directly down regulate MMP-9 expression. Bioinformatics tool analysis showed that hsa-mir-491 may target MMP-9 and has binding sites in its 3’ UTR. Luciferase reporter assay confirms the direct regulation of MMP-9 by hsa-miR-491. miRNA over expressing stable cell lines were established by lentiviral transduction of MDA-MB-231 cells with hsa-mir-491 lenti-viral vector construct. qRT-PCR studies showed down regulation of MMP-9 mRNA in miRNA over expressing cells lines compared to the normal MDA-MB-231 cells. Even though the miRNA did not have any effect on cell cycle profiles, hsa-miR-491 over expressing stable cell line showed significantly low migratory potential in assays indicating the therapeutic potential of this micorRNA as a novel means of controlling breast cancer metastasis. Our results provide the first evidence for inhibition of MMP-9 by hsa-mir-491 in breast cancer cells.
Sanu K Shaji, Damu Sunil Kumar, Drishya G, Dr. Bipin G. Nair, and Geetha B. Kumar, “MicroRNA-491 Functions to Down Regulate Gelatinase B and Inhibit Cell Migration in MDA-MB-231 Triple Negative Breast Cancer Cells”, in The XXXIX All India Cell Biology Conference , 2015.