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Updated: Mar 1, 2026

Methyl-binding DNA capture Sequencing for Patient Tissues
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CRY2 is suppressed by FOXM1 mediated promoter hypermethylation in breast cancer

Lingling Liu1, Hong Shen2, Yang Wang3

  • 1Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.

Biochemical and Biophysical Research Communications
|June 6, 2017
PubMed

Insights

Loss of CRY2 is linked to aggressive breast cancer. FOXM1 suppresses CRY2 via methylation, and high CRY2 predicts better outcomes in ER+ breast cancer patients, suggesting a new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Loss of CRY2 is associated with aggressive breast cancer phenotypes.
  • The mechanisms of CRY2 downregulation and its prognostic significance in breast cancer remain unclear.

Purpose of the Study:

  • To investigate the mechanism of CRY2 downregulation in breast cancer.
  • To evaluate the prognostic value of CRY2 expression in breast cancer patients.

Main Methods:

  • Data mining of the TCGA breast cancer cohort (TCGA-BRCA).
  • In vitro experiments involving demethylation treatment (5-AZA-dC) and gene manipulation (overexpression/knockdown) of FOXM1.
  • Bioinformatic analysis to predict transcription factor binding sites.
  • Correlation analysis (Pearson's r) and Cox proportional hazards model for prognostic evaluation using bc-GenExMiner 4.0.

Main Results:

  • CRY2 expression varied by breast cancer subtype (Luminal A highest, Basal-like lowest) and ER status (ER+ higher than ER-).
  • Demethylation restored CRY2 expression, and FOXM1 was found to be a negative regulator of CRY2, suppressing its expression via promoter methylation.
  • High CRY2 expression independently predicted a reduced risk of metastatic relapse (MR) in ER+ breast cancer patients.

Conclusions:

  • FOXM1 acts as a negative regulator of CRY2 in breast cancer by enhancing promoter methylation.
  • High CRY2 expression is an independent predictor of favorable MR-free survival in ER+ breast cancer patients.
  • CRY2 may serve as a potential prognostic biomarker and therapeutic target in ER+ breast cancer.
Keywords:
Breast cancerCRY2FOXM1MethylationPrognosis

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