NDLI: The circadian gene CRY2 is associated with breast cancer aggressiveness possibly via epigenomic modifications

Content Provider	Springer Nature Link
Author	Mao, Yingying Fu, Alan Hoffman, Aaron E. Jacobs, Daniel I. Jin, Mingjuan Chen, Kun Zhu, Yong
Copyright Year	2015
Abstract	Although the role of core circadian gene cryptochrome 2 (CRY2) in breast tumorigenesis has been demonstrated, the correlations of CRY2 with clinical parameters in breast cancer patients and its involvement in epigenetic processes such as DNA methylation remain relatively unexplored. In the current study, we first queried the Oncomine database and the Gene Expression-Based Outcome for Breast Cancer Online (GOBO) database to identify associations between CRY2 expression levels and clinical parameters in breast cancer patients. We then silenced CRY2 in vitro and performed a genome-wide methylation array to determine the epigenetic impact of CRY2 silencing. The Ingenuity Pathway Analysis software was used to further explore the genes exhibiting altered methylation identified using the array. We found that CRY2 was frequently down-regulated in breast cancer tissue compared to adjacent normal tissue or breast tissue from healthy controls. Lower CRY2 expression was associated with estrogen receptor (ER)-negativity (P < 0.0001), higher tumor grade (P < 0.0001), and shorter overall survival time in breast cancer patients (HR = 1.44, 95 % confidence interval (CI) 1.09–1.91). Genome-wide methylation analysis showed that a total of 515 CpG sites were hypermethylated following CRY2 knockdown, while 730 sites were hypomethylated. The pathway analysis revealed several cancer-relevant networks with genes exhibiting significantly altered methylation following CRY2 silencing. These findings suggest that the core circadian gene CRY2 is associated with breast cancer progression and prognosis, and that knockdown of CRY2 causes the epigenetic dysregulation of genes involved in cancer-relevant pathways, which provide further evidence supporting a role of the circadian system in breast tumorigenesis.
Starting Page	3533
Ending Page	3539
Page Count	7
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	36
Issue Number	5
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2015-03-05
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	CRY2 Breast cancer Biomarker DNA methylation Network analysis Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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