Vitamin D Suppresses Ovarian Cancer Growth and Invasion by Targeting Long Non-Coding RNA CCAT2

Int J Mol Sci. 2020 Mar 27;21(7):2334. doi: 10.3390/ijms21072334.

Abstract

Ovarian cancer is the most deadly gynecologic cancer among women worldwide. Poor response to current treatment makes it necessary to discover new diagnostic biomarkers to detect the cancer early and develop new and effective prevention strategies. Calcitriol, the active metabolite of vitamin D, protects against multiple cancers through unelucidated mechanisms. The oncogenic long non-coding RNA (lncRNA) CCAT2 (colon cancer associated transcript 2) is overexpressed in ovarian cancer. Here, we foundd that calcitriol inhibited CCAT2 expression in ovarian cancer cell lines. Treatment with calcitriol inhibited ovarian cancer cell proliferation, migration, and invasion. As a result of CCAT2 inhibition, calcitriol decreased the binding of transcription factor TCF7L2 (TCF4) to the MYC promoter, resulting in the repression of c-Myc protein expression. Our results suggest a novel anti-cancer mechanism of vitamin D by targeting CCAT2 in ovarian cancer. The findings may help develop vitamin D as a practical and inexpensive nutraceutical for ovarian cancer prevention.

Keywords: CCAT2; cancer prevention; long non-coding RNA; ovarian cancer; vitamin D.

MeSH terms

  • Calcitriol / pharmacology
  • Carcinoma, Ovarian Epithelial / prevention & control*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genes, myc
  • Humans
  • Oncogenes
  • Ovarian Neoplasms / prevention & control*
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism*
  • Transcription Factor 7-Like 2 Protein / metabolism
  • Transcription Factors
  • Vitamin D / pharmacology*
  • Wound Healing

Substances

  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors
  • long non-coding RNA CCAT2, human
  • Vitamin D
  • Calcitriol