miR-129-5p inhibits gemcitabine resistance and promotes cell apoptosis of bladder cancer cells by targeting Wnt5a
miR-129-5p inhibits gemcitabine resistance and promotes cell apoptosis of bladder cancer cells by targeting Wnt5a
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DOI：
10.1007/s11255-018-1959-x
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发表时间：
2018-10-01
影响因子：
2
通讯作者：
Wang, Qian
中科院分区：
文献类型：
--
作者：
Cao, Jingyi;Wang, Qichao;Wang, Qian
目的吉西他滨耐药是膀胱癌有效治疗的主要障碍。本研究旨在探讨miR-129- 5 p在膀胱癌细胞吉西他滨耐药中的作用及其机制。采用实时定量PCR（qRT-PCR）检测miR-129- 5 p水平和基因mRNA表达。MTT法检测细胞活力，流式细胞仪检测细胞凋亡，Western blot检测基因蛋白水平。结果miR-129 - 5 p表达下调与膀胱癌细胞及组织吉西他滨耐药相关。我们还观察到miR-129- 5 p的恢复可以显著增加细胞对吉西他滨的敏感性并促进细胞凋亡。结论miR-129 - 5 p和Wnt 5a可能是克服膀胱癌吉西他滨耐药的新靶点。
Objectives Gemcitabine resistance is a major obstacle for effective treatment of bladder cancer. This study was aimed to investigate the potential role of miR-129-5p in the development of gemcitabine resistance in bladder cancer cells and its underlying mechanism.Methods The IC50 for gemcitabine in 20 bladder cancer cells was first profiled from Genomics of Drug Sensitivity in Cancer. miR-129-5p level and gene mRNA expression were detected using quantitative real-time PCR (qRT-PCR). Cell viability, apoptosis, and gene protein level were assessed by MTT, flow cytometry, and Western blot, respectively. Regulatory relationship between Wnt5a and miR-129-5p was determined using luciferase reporter assay.Results We found that down-regulated miR-129-5p level contributed to gemcitabine resistance in bladder cancer cells and tissues. We also observed restoration of miR-129-5p could significantly increase cell sensitivity to gemcitabine and promote cell apoptosis. Mechanism analysis revealed that Wnt5a is a direct target gene of miR-129-5p and knock-down of Wnt5a reversed gemcitabine resistance.Conclusions Taken together, our findings indicate that miR-129-5p and Wnt5a may be novel therapeutic targets for overcoming gemcitabine resistance in bladder cancer treatment.