Cancer Management and Research (Oct 2018)
Non-coding RNA NEAT1/miR-214-3p contribute to doxorubicin resistance of urothelial bladder cancer preliminary through the Wnt/β-catenin pathway
Abstract
Yan Guo,1–3 Hui Zhang,4 Dalong Xie,5 Xuanhao Hu,6 Rongbo Song,1–3 Li Zhu1–3 1Department of Central Laboratory, School of Stomatology, China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Key Laboratory of Oral Disease of Liaoning Province, Shenyang, Liaoning, People’s Republic of China; 3Department of Oral Biology, School of Stomatology, China Medical University, Shenyang, Liaoning, People’s Republic of China; 4Department of Urinary Surgery, Shengjing Hospital, China Medical University, Shenyang, People’s Republic of China; 5Department of Anatomy, College of Basic Medicine, China Medical University, Shenyang, People’s Republic of China; 6Department of Neurobiology, China Medical University, Shenyang, Liaoning, People’s Republic of China Background: 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.Methods: 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.Results: 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.Conclusion: 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. Keywords: nuclear-enriched abundant transcript 1, miR-214-3p, urothelial bladder cancer, doxorubicin resistance, Wnt/β-catenin pathway
