Hsa-microRNA-1249-3p/Homeobox A13 axis modulates the expression of β-catenin gene in human epithelial cells

Sci Rep. 2023 Dec 18;13(1):22872. doi: 10.1038/s41598-023-49837-0.

Abstract

Intercellular adhesion is a key function for epithelial cells. The fundamental mechanisms relying on epithelial cell adhesion have been partially uncovered. Hsa-microRNA-1249-3p (hsa-miR-1249-3p) plays a role in the epithelial mesenchymal transition in carcinoma cells, but its physiological function in epithelial cells is unknown. We aimed to investigate the role and molecular mechanisms of hsa-miR-1249-3p on epithelial cell functions. Hsa-miR-1249-3p was overexpressed in human epithelial cells and uterine cervical tissues, compared to cervical carcinoma cells and precancerous tissues, respectively. Hsa-miR-1249-3p was analyzed to verify its regulatory function on Homeobox A13 (HOXA13) target gene and its downstream cell adhesion gene β-catenin. Functional experiments indicated that hsa-miR-1249-3p inhibition prompted the mRNA and protein overexpression of HOXA13 which, in turn, led to the β-catenin protein expression. Moreover, hsa-miR-1249-3p inhibition induced a strong colony forming ability in epithelial cells, suggesting the miR involvement in cell adhesion machinery. These data indicate that hsa-miR-1249-3p regulates the expression of HOXA13 and its downstream cell adhesion gene β-catenin, possible resulting in cell adhesion modification in epithelial cells. This study will allow the set-up of further investigations aimed at exploring the relationship between the hsa-miR-1249-3p/HOXA13 axis and downstream cell adhesion genes.

MeSH terms

  • Carcinoma* / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Epithelial Cells / metabolism
  • Gene Expression Regulation, Neoplastic
  • Genes, Homeobox
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • beta Catenin
  • homeobox protein HOXA13
  • MicroRNAs
  • MIRN1249 microRNA, human
  • CTNNB1 protein, human