RNA-Binding Protein MEX3A Interacting with DVL3 Stabilizes Wnt/β-Catenin Signaling in Endometrial Carcinoma

Int J Mol Sci. 2022 Dec 29;24(1):592. doi: 10.3390/ijms24010592.

Abstract

Disease recurrence and metastasis lead to poor prognosis in patients with advanced endometrial carcinoma (EC). RNA-binding proteins (RBPs) are closely associated with tumor initiation and metastasis, but the function and molecular mechanisms of RBPs in EC are unclear. RBPs were screened and identified using the TCGA, GEO, and RBPTD databases. The effect of MEX3A on EC was verified by in vitro and in vivo experiments. Gene set enrichment analysis (GSEA), immunofluorescence (IF), and co-immunoprecipitation (Co-IP) were used to identify potential molecular mechanisms of action. We identified 148 differentially expressed RBPs in EC. MEX3A was upregulated and related to poor prognosis in patients with EC. In vitro and vivo experiments demonstrated that MEX3A promoted the growth, migration, and invasion capacities of EC cells. Mechanistically, DVL3, a positive regulator of the Wnt/β-catenin pathway, also increased the proliferation and metastasis of EC cells. MEX3A enhanced EMT and played a pro-carcinogenic role by interacting with DVL3 to stabilize β-catenin and upregulated the expression of its downstream target genes. MEX3A is upregulated in EC and promotes tumor progression by activating EMT and regulating the Wnt/β-catenin pathway via DVL3. MEX3A may therefore be a novel therapeutic target for EC.

Keywords: DVL3; MEX3A; RBP; Wnt/β-catenin; endometrial carcinoma.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Dishevelled Proteins* / genetics
  • Dishevelled Proteins* / metabolism
  • Endometrial Neoplasms* / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Recurrence, Local / genetics
  • Phosphoproteins / metabolism
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism
  • Wnt Signaling Pathway* / genetics
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • beta Catenin
  • Dishevelled Proteins
  • DVL3 protein, human
  • MEX3A protein, human
  • Phosphoproteins
  • RNA-Binding Proteins