Long non-coding RNA DANCR promotes malignant phenotypes of bladder cancer cells by modulating the miR-149/MSI2 axis as a ceRNA.
Long non-coding RNA DANCR promotes malignant phenotypes of bladder cancer cells by modulating the miR-149/MSI2 axis as a ceRNA.
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长非编码RNA DANCR通过作为ceRNA调节miR-149/MSI2轴促进膀胱癌细胞的恶性表型
DOI：
10.1186/s13046-018-0921-1
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发表时间：
2018-11-12
期刊：
影响因子：
--
通讯作者：
Zhou L
中科院分区：
文献类型：
--
作者：
Zhan Y;Chen Z;Li Y;He A;He S;Gong Y;Li X;Zhou L
越来越多的证据表明，长链非编码RNA（lncRNAs）是潜在的生物标志物，在肿瘤发生和发展过程中发挥关键作用。分化拮抗非蛋白编码RNA（DANCR）是一种新型的lncRNA，可作为潜在的生物标志物，并参与癌症的发生发展。然而，DANCR在膀胱癌中的临床意义和分子机制仍不清楚。
通过实时定量聚合酶链反应（Real - Time qPCR）测定了总共106例膀胱尿路上皮癌患者以及不同膀胱癌细胞系中DANCR的相对表达水平。进行了功能缺失实验以研究DANCR对膀胱癌细胞增殖、迁移、侵袭和致瘤性的生物学作用。进行了全面的转录分析、RNA荧光原位杂交（RNA - FISH）、双荧光素酶报告基因检测和蛋白质印迹法（western blot）以探索DANCR功能的分子机制。
在本研究中，我们发现DANCR在膀胱癌中显著上调。此外，DANCR表达增加与更高的组织学分级和晚期TNM分期呈正相关。进一步的实验表明，敲低DANCR可抑制膀胱癌细胞的恶性表型和上皮 - 间质转化（EMT）。从机制上讲，我们发现DANCR主要分布在细胞质中，DANCR作为一种微小RNA（miRNA）海绵，通过吸附miR - 149正向调节Musashi RNA结合蛋白2（MSI2）的表达，进而促进膀胱癌细胞的恶性表型，从而在膀胱癌发病机制中发挥致癌作用。
本研究首次证明DANCR在膀胱癌细胞中起关键的调节作用，并且DANCR可能作为膀胱癌潜在的诊断生物标志物和治疗靶点。
本文的网络版（10.1186/s13046 - 018 - 0921 - 1）包含补充材料，授权用户可获取。
BackgroundAccumulating evidences have indicated that long non-coding RNAs (lncRNAs) are potential biomarkers that play key roles in tumor development and progression. Differentiation antagonizing non-protein noding RNA (DANCR) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancers. However, the clinical significance and molecular mechanism of DANCR in bladder cancer is still unknown.MethodsThe relative expression level of DANCR was determined by Real-Time qPCR in a total of 106 patients with urothelial bladder cancer and in different bladder cancer cell lines. Loss-of-function experiments were performed to investigate the biological roles of DANCR on bladder cancer cell proliferation, migration, invasion and tumorigenicity. Comprehensive transcriptional analysis, RNA-FISH, dual-luciferase reporter assay and western blot were performed to explore the molecular mechanisms underlying the functions of DANCR.ResultsIn this study, we found that DANCR was significantly up-regulated in bladder cancer. Moreover, increased DANCR expression was positively correlated with higher histological grade and advanced TNM stage. Further experiments demonstrated that knockdown of DANCR inhibited malignant phenotypes and epithelial-mesenchymal transition (EMT) of bladder cancer cells. Mechanistically, we found that DANCR was distributed mostly in the cytoplasm and DANCR functioned as a miRNA sponge to positively regulate the expression of musashi RNA binding protein 2 (MSI2) through sponging miR-149 and subsequently promoted malignant phenotypes of bladder cancer cells, thus playing an oncogenic role in bladder cancer pathogenesis.ConclusionThis study is the first to demonstrate that DANCR plays a critical regulatory role in bladder cancer cell and DANCR may serve as a potential diagnostic biomarker and therapeutic target of bladder cancer.
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