Presentation Authors: Yonghao Zhan*, Zhicong Chen, Shiming He, Xuesog Li, Liqun Zhou, Beijing, China, People's Republic of
Introduction: Accumulating evidence has 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. Here, we elucidated the function and possible molecular mechanisms of the effect of DANCR on the biological behaviors of bladder cancer cells.
Methods: The expression level of DANCR was determined by RT-qPCR in a total of 106 patients with urothelial bladder cancer and validated by online datasets. 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: DANCR was highly expressed in bladder cancer and positively correlated with advanced tumor stage and poor prognosis. Inhibition of DANCR repressed cell proliferation, migration and invasion in vitro. Moreover, inhibition of DANCR also elicited delayed tumor growth of xenograft in vivo. Mechanistically, RNA-FISH results revealed that DANCR was mainly distributed in the cytoplasm and the bio-information analysis revealed that DANCR and MSI2 have common putative binding sites with miR-149. Further experimental results demonstrated that DANCR functions as a miRNA sponge to positively regulate MSI2 expression by sponging the miR-149. Furthermore, overexpression of MSI2 reversed the malignant phenotype inhibition induced by silencing DANCR.
Conclusions: Taken together, DANCR is a promising novel prognosis biomarker in bladder cancer. That DANCR promotes bladder cancer growth and metastasis through regulating MSI2 may represent a target for clinical intervention.
Source of Funding: This work was supported by the National Key R&D Program of China (2016YFC0902601); the National Natural Science Foundation of China (81672546, 81602253, 81772703); the Natural Science Foundation of Beijing (71772219, 7152146).