LncRNA KCNQ1OT1 promotes oxaliplatin resistance of ovarian cancer cells through upregulating Bmi1 by sponging miR-128-3p

The long non-coding RNA (lncRNA) KCNQ1OT1 exerts oncogenic functions in human cancers, including ovarian cancer (OC). However, the potential role and detailed mechanism of KCNQ1OT1 in modulating chemoresistance in OC remain unclear. Herein, it showed that KCNQ1OT1 expression was upregulated in OC tissues and tissues from oxaliplatin (OHP)-resistant OC patients. KCNQ1OT1 exhibited oncogenic functions in OVCAR3 and A2780 OC cell lines with increased sensitivity of drug-resistant OC cells against OHP. miR-128-3p was identified as a target of KCNQ1OT1 which negatively regulated the expression levels of the former. Overexpression of miR-128-3p reversed the oncogenic effects of KCNQ1OT1 in OC cells and OHP sensitivity. miR-128-3p main target B lymphoma Mo-MLV insertion region 1 homolog (Bmi1) and negatively regulated its expression, while later positively regulated by KCNQ1OT1. The mouse xenograft tumor experiments in vitro and in vivo have demonstrated that KCNQ1OT1 promoted OC progression and oxaliplatin resistance by upregulating Bmi1 by involving miR-128-3p. Taken together, KCNQ1OT1 acts as a molecular target to bind miR-128-3p and regulates the expression levels of Bim1 in cancer cells that consequently promote tumor progression and OHP resistance in OC. The KCNQ1OT1-miR-128-3p-Bmi1 pathway may represent novel targets for OC treatment.