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

Autor: Hui Zhang, Rongbo Song, Dalong Xie, Li Zhu, Yan Guo, Xuanhao Hu
Rok vydání: 2018
Předmět:
Zdroj: Cancer Management and Research
ISSN: 1179-1322
Popis: 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
Databáze: OpenAIRE