LncRNA RBMS3-AS3 promotes ovarian cancer progression by regulating QKI and RBFOX2

Abstract

Long non-coding RNAs (lncRNAs) exert pivotal regulatory functions in the malignant progression of ovarian cancer. Despite this, the biological roles and underlying molecular mechanisms of lncRNA RBMS3-AS3 in ovarian cancer pathogenesis have yet to be fully elucidated. RBMS3-AS3 is highly expressed in ovarian cancer, with its expression correlated with poor overall survival in patients. It was predominantly localized in the cytoplasm of ovarian cancer cells. Silencing of lncRNA RBMS3-AS3, RBFOX2 (RNA binding fox-1 homolog 2), or QKI (Quaking) suppressed cell proliferation, migration, and invasive capacity, whereas their overexpression enhanced these oncogenic behaviors. Bioinformatic analyses identified QKI and RBFOX2 as potential downstream targets of RBMS3-AS3, and RNA pull-down and RIP assays verified the direct interaction between RBMS3-AS3 and RBFOX2/QKI. Moreover, silencing RBMS3-AS3 accelerated proteasomal degradation of QKI and RBFOX2 proteins via enhancing their ubiquitination. Importantly, simultaneous co-knockdown of QKI and RBFOX2 rescued the oncogenic effects of RBMS3-AS3 overexpression. RBMS3-AS3 promotes ovarian cancer malignant progression by physically binding to and stabilizing the oncoproteins QKI and RBFOX2. Collectively, these findings suggest that RBMS3-AS3 may represent a promising novel therapeutic target for ovarian cancer intervention.