Paeoniflorin inhibits colorectal cancer cell stemness through the miR-3194-5p/catenin beta-interacting protein 1 axis

Kaohsiung J Med Sci. 2023 Oct;39(10):1011-1021. doi: 10.1002/kjm2.12736. Epub 2023 Aug 2.

Abstract

Paeoniflorin (PF) is a natural plant ingredient with remarkable antitumor effects. Herein, we investigated the biological effects and mechanism of PF in colorectal cancer (CRC) cell stemness. The messenger RNA (mRNA) and protein expressions were assessed using quantitative real-time polymerase chain reaction and western blot. The viability, proliferation, and migration and invasion of CRC cells were evaluated using cell counting kit-8, clone-formation, and transwell migration and invasion assays, respectively. The sphere-formation capacity was determined using the sphere-formation assay. A dual-luciferase reporter gene assay was employed to analyze the interaction between miR-3194-5p and catenin beta-interacting protein 1 (CTNNBIP1). The viability, migration, invasion, epithelial-mesenchymal transition, and stemness of CRC cells were repressed by PF. MiR-3194-5p was upregulated in CRC tissues and cells. MiR-3194-5p knockdown suppressed CRC cell stemness, while miR-3194-5p overexpression had the opposite effect. In addition, the inhibition of CRC cell stemness caused by PF was eliminated by miR-3194-5p overexpression. CTNNBIP1 functioned as the target of miR-3194-5p, whose knockdown abrogated the repression of CRC cell stemness and Wnt/β-catenin signaling activation by PF.PF regulated the miR-3194-5p/CTNNBIP1/Wnt/β-catenin axis to repress CRC cell stemness.

Keywords: CTNNBIP1; colorectal cancer; miR-3194-5p; paeoniflorin; stemness.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • MicroRNAs
  • peoniflorin
  • beta Catenin