Crocin suppresses breast cancer cell proliferation by down-regulating tumor promoter miR-122-5p and up-regulating tumor suppressors FOXP2 and SPRY2

Environ Toxicol. 2023 Jul;38(7):1597-1608. doi: 10.1002/tox.23789. Epub 2023 Mar 29.

Abstract

Crocin has been reported to have antitumor activity in several tumors including breast cancer. Nevertheless, the mechanism of action of crocin on breast cancer remains unclear. The cytotoxicity of crocin was evaluated by CCK-8 assay. Cell proliferation was assessed using EdU incorporation assay and western blot analysis. Breast cancer-related genes were extracted from GEPIA. miR-122-5p targets were predicted using Targetscan, starbase, and miRDB softwares. Luciferase reporter assay was employed to confirm whether miR-122-5p targeted sprouty2 (SPRY2) and forkhead box P2 (FOXP2). Results showed that crocin exhibited cytotoxicity and suppressed the proliferation in breast cancer cells. miR-122-5p was upregulated in breast cancer tissues and cells. Crocin suppressed miR-122-5p to block the proliferation of breast cancer cells. Seven targets of miR-122-5p were identified in breast cancer. SPRY2 and FOXP2 were selected for further experiments due to their involvement in breast cancer. miR-122-5p targeted SPRY2 and FOXP2 to inhibit their expression. miR-122-5p knockdown restrained breast cancer cell proliferation by targeting SPRY2 and FOXP2. Additionally, crocin increased SPRY2 and FOXP2 expression by inhibiting miR-122-5p expression. Together, our results suggested that crocin inhibited proliferation of breast cancer cells through decreasing miR-122-5p expression and the subsequent increase of SPRY2 and FOXP2 expression.

Keywords: FOXP2; SPRY2; breast cancer; crocin; miR-122-5p; proliferation.

MeSH terms

  • Breast Neoplasms* / metabolism
  • Carcinogens
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism

Substances

  • MicroRNAs
  • crocin
  • Carcinogens
  • SPRY2 protein, human
  • Membrane Proteins
  • Intracellular Signaling Peptides and Proteins
  • FOXP2 protein, human
  • Forkhead Transcription Factors
  • MIRN122 microRNA, human