Exosomal lncRNA USP30‐AS1 activates the Wnt/β‐catenin signaling pathway to promote cervical cancer progression via stabilization of β‐catenin by USP30

Abstract

AbstractCervical cancer (CC) remains a major cause of cancer‐related mortality among women globally. Long noncoding RNAs (lncRNAs) play crucial regulatory roles in various cancers, including CC. This study investigates the function of a novel lncRNA, USP30 antisense RNA 1 (USP30‐AS1), in CC tumorigenesis. We analyzed USP30‐AS1 expression using RT‐qPCR and conducted in vitro loss‐of‐function assays, as well as in vivo assays, to evaluate the effects of USP30‐AS1 silencing on CC cell growth and migration. Additional mechanistic experiments, including RNA pull‐down, RNA immunoprecipitation (RIP), and co‐immunoprecipitation (Co‐IP) assays, were performed to elucidate the regulatory mechanisms influenced by USP30‐AS1. We discovered that USP30‐AS1 is overexpressed in CC tissues and cells. Silencing USP30‐AS1 significantly reduced cell proliferation, migration, invasion, and tumor growth. Moreover, USP30‐AS1 was found to modulate the expression of ubiquitin‐specific peptidase 30 (USP30) by sponging microRNA‐2467‐3p (miR‐2467‐3p) and recruiting the FUS RNA binding protein (FUS), thereby stabilizing β‐catenin and activating the Wnt/β‐catenin signaling pathway. These findings suggest that USP30‐AS1 enhances CC cell growth and migration through the miR‐2467‐3p/FUS/USP30 axis, highlighting its potential as a biomarker for CC.