2015
DOI: 10.1158/0008-5472.can-14-2341
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Cytidine Deaminase Axis Modulated by miR-484 Differentially Regulates Cell Proliferation and Chemoresistance in Breast Cancer

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 prolifer… Show more

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Cited by 74 publications
(65 citation statements)
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“…miR-484 was originally discovered to be associated with resistance to chemotherapeutic agents in cancer [38]. This year, an aberrant expression of miR-484 has also been described in high-fat-diet-induced tumours, with a fluctuant miR-484 overexpression during feeding [39].…”
Section: Discussionmentioning
confidence: 99%
“…miR-484 was originally discovered to be associated with resistance to chemotherapeutic agents in cancer [38]. This year, an aberrant expression of miR-484 has also been described in high-fat-diet-induced tumours, with a fluctuant miR-484 overexpression during feeding [39].…”
Section: Discussionmentioning
confidence: 99%
“…MDA-MB-231 gemcitabine-resistant cells (231/GEM) were generously gifted by Xiaoli Yang from Key Laboratory of Breast Cancer in Fudan University Shanghai Cancer Center and they were generated by exposure to gradually increased concentrations of gemcitabine for more than one year [8]. Cells were cultured in DMEM supplemented with 10% fetal bovine serum (FBS) at 37°C in a humidified atmosphere with 5% CO 2 .…”
Section: Methodsmentioning
confidence: 99%
“…CDA dysfunction has pathological implications, particularly in cancers, in which CDA activity might be either up-or downregulated, affecting the sensitivity of cancer cells to nucleotide analogs, such as gemcitabine (Ye et al, 2015;Zauri et al, 2015;Serdjebi et al, 2015). The importance of CDA defects and, more broadly, of pyrimidine pool disequilibrium, is illustrated by Bloom syndrome, a rare genetic disease displaying one of the strongest known correlations between chromosomal instability and an increase in cancer risk (German, 1997).…”
Section: Introductionmentioning
confidence: 99%