Steroid hormone calcitriol and its analog tacalcitol inhibit miR-125b expression in a human breast cancer MCF-7 cell line

Steroids. 2019 Jan:141:70-75. doi: 10.1016/j.steroids.2018.11.014. Epub 2018 Nov 29.

Abstract

MiR-125b belongs to the class of microRNAs, which are short endogenous non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Recently, it was reported that miR-125b was found to promote migration and invasion of MCF-7 cells and was involved in chemotherapeutic resistance. Decreasing miR-125b expression would have potential therapeutic significance in preventing dissemination of breast cancer cells. The objective of this study was to evaluate miR-125b expression levels in MCF-7 cells following treatment with 1,25-dihydroxyvitamin D3 (calcitriol) and 1,24-dihydroxyvitamin D3 (tacalcitol), active metabolite and synthetic analog of vitamin D3, respectively. We found that treatment with both calcitriol and tacalcitol caused a decrease in miR-125b expression. In addition, treatment with calcitriol and tacalcitol resulted in an increase in the level of pro-apoptotic BAK1 protein encoded by the target gene of miR-125b. We are discussing the putative mechanism of inhibition of the miR-125b expression by vitamin D receptor (VDR) agonists and we suggest that calcitriol and tacalcitol may be used as a miR-125b inhibitor in breast cancer cells expressing VDR.

Keywords: BAK1; Calcitriol; MCF-7 cells; Tacalcitol, PRI-2191; miR-125b; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Calcitriol / pharmacology*
  • Cell Proliferation / drug effects
  • Dihydroxycholecalciferols / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • MCF-7 Cells
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Molecular Conformation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Dihydroxycholecalciferols
  • MIRN125 microRNA, human
  • MicroRNAs
  • 1 alpha,24-dihydroxyvitamin D3
  • Calcitriol