MicroRNA-532-3p modulates colorectal cancer cell proliferation and invasion via suppression of FOXM1

Abstract Forkhead-box M1 (FOXM1) is a proliferation-associated transcription factor, overexpressed in almost all the cancers. Naturally, the mechanisms of FOXM1 regulation have been under investigation. Previously, we showed that FOXM1 binds to promoters of certain microRNAs. Database mining led to several microRNAs that might interact with FOXM1 3’UTR. The interactions between shortlisted microRNAs and FOXM1 3’UTR was quantitated by dual luciferase reporter assay. MicroRNA-532-3p interacted with 3’UTR of FOXM1 mRNA transcript most efficiently. MicroRNA-532-3p was ectopically overexpressed in colorectal cancer cell lines, leading to reduced transcript and protein levels of FOXM1 and cyclin B1, a direct transcriptional target of FOXM1. Flow cytometry analysis revealed an unaltered cell cycle. A clonogenic assay was conducted that revealed a decline in the ability of cells to form colonies. Additionally, wound healing assay and matrigel invasion assays were carried out. Significant reduction in migratory and invading cell numbers were observed, which were reinforced at molecular levels by the altered transcript and protein levels of the conventional EMT markers E-cadherin and vimentin. Overall, this study identifies the interaction between microRNA-532-3p and FOXM1 3’UTR, leading to reduced protein levels. Ectopic expression of miR-532-3p leads to suppression in cellular proliferation, migration and invasion in CRC cells.