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

Biotechnol J. 2024 Jul;19(7):e2300653. doi: 10.1002/biot.202300653.

Abstract

Cervical 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.

Keywords: FUS; USP30; USP30‐AS1; cervical cancer; miR‐2467‐3p.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation* / genetics
  • Disease Progression
  • Exosomes / genetics
  • Exosomes / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / metabolism
  • Uterine Cervical Neoplasms* / pathology
  • Wnt Signaling Pathway* / genetics
  • beta Catenin* / genetics
  • beta Catenin* / metabolism

Substances

  • beta Catenin
  • CTNNB1 protein, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Usp30 protein, human