Home » Key Clinical Research Articles Global Medical Discovery » Cytidine Deaminase Axis Modulated by miR-484 Differentially Regulates Cell Proliferation and Chemoresistance in Breast Cancer

Cytidine Deaminase Axis Modulated by miR-484 Differentially Regulates Cell Proliferation and Chemoresistance in Breast Cancer

Ye FG1, Song CG2, Cao ZG3, Xia C4, Chen DN5, Chen L3, Li S3, Qiao F3, Ling H3, Yao L3, Hu X6, Shao ZM3.

Cancer Res. 2015 Apr 1;75(7):1504-15.

1Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Breast Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, China.

2Department of Breast Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, China. [email protected] [email protected]

3Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

4The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

5Department of Breast Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, China.

6Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. [email protected] [email protected]

Abstract

There has been little study of how the evolution of chemoresistance  in cancer affects other aspects of disease pathogenesis. Here, we show that an important chemoresistance axis driven by cytidine deaminase (CDA) also acts to suppress cell-cycle progression by regulating cyclin E-CDK2 signaling. We found that CDA was regulated by miR-484 in a gemcitabine-resistant model of breast cancer. Elevating miR-484 expression reversed the CDA effects, thereby enhancing gemcitabine sensitivity, accelerating cell proliferation, and redistributing cell-cycle progression. Conversely, elevating CDA to restore its expression counteracted the chemosensitization and cell proliferative effects of miR-484. In clinical specimens of breast cancer, CDA expression was frequently downregulated and inversely correlated with miR-484 expression. Moreover, high expression of CDA was associated with prolonged disease-free survival in studied cohorts. Collectively, our findings established that miR-484-modulated CDA has a dual impact in promoting chemoresistance and suppressing cell proliferation in breast cancer, illustrating the pathogenic tradeoffs associated with the evolution of chemoresistance in this malignant disease. Cancer Res; 75(7); 1504-15. ©2015 AACR.

©2015 American Association for Cancer Research.

Go To PubMed