MiR-507 inhibits the progression of gastric carcinoma via targeting CBX4-mediated activation of Wnt/β-catenin and HIF-1α pathways

Clin Transl Oncol. 2022 Oct;24(10):2021-2028. doi: 10.1007/s12094-022-02862-3. Epub 2022 Jul 11.

Abstract

Purpose: Gastric carcinoma (GC) is a common malignant disease with high morbidity and mortality. MiR-507 has been confirmed as a tumor inhibitor which can suppress the progression of multiple cancers while its role in GC remains unknown.

Methods: In this study, the expression levels of miR-507 in the GC tissues and cells were observed by qRT-PCR, and CCK-8 assay, transwell asssay and TUNEL assay were used to observe the function of miR-507 on GC. The miRNA database and dual-luciferase reporter assay were used to investigate the downstream target of miR-507. Moreover, the activities of Wnt/β-catenin and HIF-1α pathways were observed by western blot.

Results: The results showed that miR-507 was significantly downregulated in GC tissues and cell lines, and miR-507 upregulation effectively inhibited the proliferation and invasion and induced the apoptosis of GC cells. CBX4 was a downstream target of miR-507, and CBX4 could reverse the effects of miR-507 on the GC cells. Moreover, it was determined that miR-507 could inhibit CBX4 expression to suppress the activation of Wnt/β-catenin and HIF-1α pathways.

Conclusions: In conclusion, it suggests that miR-507 could inhibit the progression of GC via regulating CBX4-mediated activation of Wnt/β-catenin and HIF-1α pathways.

Keywords: CBX4; Gastric carcinoma; HIF-1α; Wnt/β-catenin; miR-507.

MeSH terms

  • Carcinoma*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Ligases
  • MicroRNAs* / genetics
  • Polycomb-Group Proteins / genetics
  • Stomach Neoplasms* / genetics
  • Wnt Signaling Pathway
  • beta Catenin / metabolism

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN507 microRNA, human
  • MicroRNAs
  • Polycomb-Group Proteins
  • beta Catenin
  • Ligases
  • CBX4 protein, human