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Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
Published on: August 12, 2015
DEC2 Serves as Potential Tumor Suppressor in Breast Carcinoma
Wentong Fang1, Qian Li1, Min Wang1
1Department of Pharmacy, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Background:
Identification of new biomarkers can facilitate the development of effective therapeutic strategies in breast cancer (BC). Data from previous studies have revealed that differentiated embryonic chondrocyte gene (DEC) 1 and DEC2 might involve in the progression of various cancer types. We explored the expression profiles and function of DEC1/2 in BC patients in this study.
Methods:
The mRNA expression of DEC1/2 in BC patients and cell lines were taken from the Oncomine and Cancer Cell Line Encyclopedia database. The prognostic impacts of DEC1/2 were mined from the bc-GenExMiner and Kaplan-Meier plotter database. The impact of DEC1/2 genomic alterations on patient survival was calculated by cBioPortal. DEC2 protein expressions were confirmed by Western blotting (WB) in 10 pairs of BC samples. In addition, DEC2 sgRNA was constructed to confirm its affection on cell viability, invasion, and colony formation.
Results:
The DEC1 and DEC2 mRNA levels are both lower in BC tissues than normal tissues. DEC1/2 expression was high in progesterone receptor (PR) positive BC patients (P = 0.0023), but low in human epidermal growth factor receptor 2 (HER2) positive patients (P < 0.0001). Lower DEC2 mRNA level has significant association with more aggressive pathogenic grade (P < 0.0001) and worse overall survival (OS) of BC patients (P = 5.2 × 10-6). Subgroup analysis showed that low DEC2 level was correlated with worse OS in estrogen receptor (ER) positive BC (P = 0.008). DEC2 (P = 0.00029) alteration was significantly correlated with worse OS in BC patients. WB results also confirmed the lower DEC2 protein levels in BC samples than their paired normal tissues. And, DEC2 silencing by sgRNA resulted in a significant increasing in cell viability, invasion, and colony formation.
Conclusion:
DEC2 might serve as a tumor suppressor, and its disfunction may involve in the tumorigenesis and indicate bad clinical outcomes in BC patients.
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