Abstract
Increasing evidences have proved that long noncoding RNAs (lncRNAs) modulate the tumorigenesis of bladder cancer involved in multiple pathophysiological processes. In the study, we investigate the role of lncRNA FOXD2-AS1 in the gemcitabine (GEM) resistant bladder cancer and explore its potential mechanism. Results showed that lncRNA FOXD2-AS1 was high-expressed in gemcitabine-resistant bladder cancer cells. In vitro experiments, FOXD2-AS1 knockdown suppressed the 50% inhibitive concentration (IC50) of gemcitabine, drug-resistance related genes (MDR1, MRP2, LRP1) expression, invasion and ABCC3 protein expression in gemcitabine-resistant bladder cancer cells (T24/GEM, 5637/GEM). In vivo of xenograft assay, FOXD2-AS1 knockdown inhibited the tumor growth of bladder cancer cells. Bioinformatics program and validation experiments confirmed that FOXD2-AS1 positively regulated ABCC3 protein through targeting miR-143, acting as a competing endogenous RNA (ceRNA). In summary, our results revealed the vital roles of FOXD2-AS1/miR-143/ABCC3 axis in gemcitabine resistance of bladder cancer cells, providing a novel therapeutic strategy for bladder cancer.
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