Abstract
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.
Highlights
Accumulating evidences have indicated that long non-coding RNAs are potential biomarkers that play key roles in tumor development and progression
Further experiments demonstrated that knockdown of Differentiation antagonizing non-protein noding RNA (DANCR) inhibited malignant phenotypes of bladder cancer cells
We found that DANCR was distributed mostly in the cytoplasm and DANCR functioned as a miRNA sponge to positively regulate musashi RNA binding protein 2 (MSI2) expression by sponging miR-149 in a Competing endogenous RNA (ceRNA)-dependent manner
Summary
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. The clinical significance and molecular mechanism of DANCR in bladder cancer is still unknown. Recent accumulating evidences have indicated that lncRNAs, such as SPRY4-IT1, UCA-1, and PANDAR, play important regulatory roles in diverse biological processes in bladder cancer [16,17,18,19,20,21,22]. Differentiation antagonizing non-protein noding RNA (DANCR, HGNC:28964) is a novel identified lncRNA located at 4q12.5 [23,24,25,26]. The biological function and underlying mechanism of DANCR in bladder cancer is completely unknown
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