Non-coding RNA NEAT1/miR-214-3p contribute to doxorubicin resistance of urothelial bladder cancer preliminary through the Wnt/β-catenin pathway

• Published in: Cancer management and research 2018-01, Vol.10, p.4371-4380
• Main Authors: Guo, Yan, Zhang, Hui, Xie, Dalong, Hu, Xuanhao, Song, Rongbo, Zhu, Li
• Format: Article
• Language: English
• Subjects: Apoptosis; Bladder cancer; Breast cancer; Chemotherapy; doxorubicin resistance; Kinases; Laboratories; MicroRNAs; miR-214-3p; Neurosciences; Nuclear-enriched abundant transcript 1; Original Research; Proteins; Surgery; Tumors; urothelial bladder cancer; WNT/β-Catenin pathway
• ISSN: 1179-1322; 1179-1322
• DOI: 10.2147/CMAR.S171126

Urothelial bladder cancer (UBC) is one of the most lethal urological malignancies in the world. Patients with UBC are routinely given chemotherapy which results in a median survival of 12-15 months. Nuclear-enriched abundant transcript 1 (NEAT1) functions as an oncogene and could be used as a therapeutic target for human UBC. However, the involvement of NEAT1 in doxorubicin (DOX) resistance of UBC has been poorly demonstrated. Quantitative Real-time PCR (qRT-PCR) was used to detect the expression levels of NEAT1 and miR-214-3p in UBC tissues and cells. Bioinformatics prediction, RNA pull-down and qRT-PCR were used to assay the regulation manner of NEAT1 and miR-214-3p. Loss/gain function of NEAT1 and miR-214-3p together with western blot, drug resistance assay and flow cytometry were used to explore the influence of NEAT1 in DOX resistance was correlative with miR-214-3p. Finally, luciferase assay system was applied to determine the Wnt/β-catenin signal activity. NEAT1 was upregulated and miR-214-3p was downregulated in DOX-resistant UBC tissues and cells. NEAT1 knockdown inhibited J82 and T24 cells to DOX chemosensitivity by negatively regulating miR-214-3p expression. NEAT1/miR-214-3p contributed to DOX resistance of UBC preliminary through the Wnt/β-catenin pathway. NEAT1 contributed to DOX resistance of UBC through the Wnt/β-catenin pathway partly by negatively regulating miR-214-3p expression. Our findings will provide a promising ncRNA targeted therapeutic strategy for UBC with DOX resistance.