MiRNA-3163 limits ovarian cancer stem-like cells via targeting SOX-2 transcription factor

Abstract

Cancer stem cells (CSCs) are pivotal in both cancer progression and the acquisition of drug resistance. MicroRNAs (miRNAs) play a crucial role in modulating CSC properties and are being explored as potential targets for therapeutic interventions. MiR-3163 is primarily known for its tumor suppressive properties in various human malignancies, with lower expression reported across different cancer types. However, its role in regulating the ovarian CSC phenotype and the underlying mechanism remain largely unknown. Here, we report a remarkable downregulation of miR-3163 in ovarian cancer stem-like cells (CSLCs). Enforced expression of miR-3163 in ovarian adherent and CSLCs, significantly disrupts the stemness phenotype. Moreover, downregulation of miR-3163 expression in ovarian cancer cells (OV2008 and OVCAR-3) inhibits the stem-like cells characterized by CD44+CD117+ expression. Sphere formation assay results reveal that overexpression of miR-3163 in ovarian cancer cells significantly inhibits spheroid formation ability, confirming the regulatory properties of miR-3163 on ovarian CSLCs. Mechanistic investigation reveals that miR-3163 depletes ovarian CSLCs via targeting SOX-2. Furthermore, we establish SOX-2 as a direct target of miR-3163 through dual-luciferase assay. Taken together, our study demonstrates that overexpression of miR-3163 could be a promising strategy for efficiently eradicating the CSC population to prevent chemoresistance and tumor relapse in ovarian cancer patients.