Hypoxia-elevated circELP3 contributes to bladder cancer progression and cisplatin resistance

作者：Yinjie Su, Weiping Yang, Ning Jiang, Juanyi Shi, Luping Chen, Guangzheng Zhong, Junming Bi, Wei Dong, Qiong Wang, Chunhui Wang, Tianxin Lin · 发表于：International Journal of Biological Sciences · 年份：2019 · DOI：10.7150/ijbs.26826 · 被引用次数：123 · 研究领域：Circular RNAs in diseases、Cardiovascular, Neuropeptides, and Oxidative Stress Research、MicroRNA in disease regulation

Hypoxia plays a critical role in cancer biology. It induces genomic instability, which in turn helps cancer cells respond adaptively to meet the needs of carcinogenesis, cancer progression and relapse. Circular RNA has not been reported among the variety of downstream factors in this adaptive response. Although a few studies have demonstrated the important role of circular RNAs in driving human bladder cancer progression, their carcinogenic roles are still under investigated. Here, we identified a hypoxia-elevated circular RNA, circELP3, that contributes to bladder cancer progression and cisplatin resistance. Decreasing the level of circELP3 via siRNA clearly reduced the in vitro proliferation and cisplatin resistance of bladder cancer cells and promoted apoptosis. Interfering with circELP3 suppressed tumor xenograft growth in nude mice in vivo. In addition, lower circELP3-expressing bladder cancer cells displayed poorer self-renewal capacity, as demonstrated by lower levels of sphere formation and stem cell marker expression. Furthermore, in human bladder cancer patients, strong correlations between a high circELP3 level and advanced tumor grade and lymph node metastasis were observed. In summary, we provide the first direct evidence that circular RNA participates in the adaptive response to hypoxia and may play a role in the progression and drug resistance of bladder cancer.