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Long non-coding RNA DANCR promotes malignant phenotypes of bladder cancer cells by modulating the miR-149/MSI2 axis as a ceRNA.

ABSTRACT: BACKGROUND:Accumulating 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. METHODS:The 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. RESULTS:In 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. CONCLUSION:This 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.

SUBMITTER: Zhan Y

PROVIDER: S-EPMC6233575 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Long non-coding RNA DANCR promotes malignant phenotypes of bladder cancer cells by modulating the miR-149/MSI2 axis as a ceRNA.

Zhan Yonghao Y Chen Zhicong Z Li Yifan Y He Anbang A He Shiming S Gong Yanqing Y Li Xuesong X Zhou Liqun L

Journal of experimental & clinical cancer research : CR 20181112 1

<h4>Background</h4>Accumulating 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.<h4>Methods</h4>The relative expression level of DANCR was de ...[more]

PMID: 30419948

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Project description:BackgroundNumerous studies proved that long non-coding RNA (lncRNA) is involved in the progression of multifarious diseases, especially in some carcinomas. As a potential tumor biomarker, plasmacytoma variant translocation 1 gene (PVT1) is involved in the development and progression of multifarious cancers. Nevertheless, the intrinsic and concrete molecular mechanism of PVT1 in bladder cancer still remained unclear, which is also the dilemma faced in many non-coding RNA studies.ResultsOur research revealed that PVT1 was significantly higher expression in bladder carcinoma specimens and cell lines. Further experiments indicated that knockdown or overexpression of PVT1 restrained or promoted the malignant phenotype and WNT/β-catenin signaling in bladder cancer cells. Meanwhile miR-194-5p was in contrast and miR-194-5p could partially reverse the function of PVT1 in malignant bladder tumor cells. As a microRNA sponge, PVT1 actively promotes the expression of b-cells lymphoma-2-associated transcription factor 1 (BCLAF1) to sponge miR-194-5p and subsequently increases malignant phenotypes of bladder cancer cells. Therefore, it performs a carcinogenic effect and miR-194-5p as the opposite function, and serves as an antioncogene in the bladder carcinomas pathogenesis.ConclusionPVT1-miR-194-5p-BCLAF1 axis is involved in the malignant progression and development of bladder carcinomas. Experiments revealed that PVT1 has a significant regulatory effect on bladder cancer (BC) and can be used as a clinical diagnostic marker and a therapeutic molecular marker for patients suffering from BC.MethodsIn urothelial bladder carcinoma specimens and cell lines, the relative expression levels of PVT1 and miR-194-5p were detected by quantitative reverse transcription PCR (RT-qPCR). Through experiments such as loss-function and over-expression, the biological effects of PVT1 and miR-194-5p on the proliferation, migration, apoptosis and tumorigenicity were explored in bladder cancer cells. Co-immunoprecipitation, proteomics experiments, dual luciferase reporter gene analysis, western blot and other methods were adopted to investigate the PVT1 potential mechanism in bladder carcinomas.

Dataset Information

Long non-coding RNA DANCR promotes malignant phenotypes of bladder cancer cells by modulating the miR-149/MSI2 axis as a ceRNA.

Publications

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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