Bioactive Vitamin D Attenuates MED28-Mediated Cell Growth and Epithelial-Mesenchymal Transition in Human Colorectal Cancer Cells

Biomed Res Int. 2022 Aug 29:2022:2268818. doi: 10.1155/2022/2268818. eCollection 2022.

Abstract

Inadequate vitamin D status may increase the risk of developing multiple types of cancer. Epidemiological studies suggest an inverse association between 25-hydroxyvitamin D3 (25(OH)D3) and malignancy, including colorectal cancer. Previous studies have suggested that MED28, a Mediator subunit involved in transcriptional regulation, is associated with the growth of colorectal cancer cells; however, its role in the progression of metastasis such as epithelial-mesenchymal transition (EMT) and cell migration of colorectal cancer is unclear at present. The aim of this study was to investigate a potentially suppressive effect of calcitriol, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), a bioactive form of vitamin D, and the role of MED28 in the progression of EMT in human colorectal cancer cells. Suppression of MED28 increased the expression of E-cadherin and reduced the expression of several mesenchymal and migration biomarkers and Wnt/β-catenin signaling molecules, whereas overexpression of MED28 enhanced the EMT features. Calcitriol suppressed the expression of MED28, and the effect of calcitriol mirrored that of MED28 silencing. Our data indicate that calcitriol attenuated MED28-mediated cell growth and EMT in human colorectal cancer cells, underlining the significance of MED28 in the progression of colorectal cancer and supporting the potential translational application of calcitriol.

MeSH terms

  • Calcitriol / pharmacology
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Mediator Complex* / genetics
  • Vitamin D* / pharmacology
  • Vitamins / pharmacology

Substances

  • MED28 protein, human
  • Mediator Complex
  • Vitamins
  • Vitamin D
  • Calcitriol