期刊
MOLECULAR CARCINOGENESIS
卷 55, 期 5, 页码 757-767出版社
WILEY
DOI: 10.1002/mc.22319
关键词
bladder cancer; apoptosis; miR-148a; cisplatin; cell cycle; DNA methyltransferase (DNMT1); doxorubicin
资金
- U.S Department of Veterans Affairs, Office of Research and Development [BX00004000 BX001079]
- National Cancer Institute [CA133209]
- UC Davis
- Biotechnology Training Program
Urothelial cell carcinoma of the bladder (UCCB) is the most common form of bladder cancer and it is estimated that approximate to 15,000 people in the United States succumbed to this disease in 2013. Bladder cancer treatment options are limited and research to understand the molecular mechanisms of this disease is needed to design novel therapeutic strategies. Recent studies have shown that microRNAs play pivotal roles in the progression of cancer. miR-148a has been shown to serve as a tumor suppressor in cancers of the prostate, colon, and liver, but its role in bladder cancer has never been elucidated. Here we show that miR-148a is down-regulated in UCCB cell lines. We demonstrate that overexpression of miR-148a leads to reduced cell viability through an increase in apoptosis rather than an inhibition of proliferation. We additionally show that miR-148a exerts this effect partially by attenuating expression of DNA methyltransferase 1 (DNMT1). Finally, our studies demonstrate that treating cells with both miR-148a and either cisplatin or doxorubicin is either additive or synergistic in causing apoptosis. These data taken together suggest that miR-148a is a tumor suppressor in UCCB and could potentially serve as a novel therapeutic for this malignancy. (c) 2015 Wiley Periodicals, Inc.
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