Long noncoding RNA FOXD2-AS1 accelerates the gemcitabine-resistance of bladder cancer by sponging miR-143.

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.