Long non-coding RNA DANCR promoted non-small cell lung cancer cells metastasis via modulating of miR-1225-3p/ErbB2 signal

Y.-F. Huang, Y. Zhang, X. Fu

Department of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China. ella99123@163.com

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• Oncology

OBJECTIVE: Currently, we aimed to illustrate the role of lncRNA differentiation antagonizing non-protein coding RNA (DANCR) and erb-b2 receptor tyrosine kinase 2 (ErbB2) in non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS: Expression of DANCR, microRNA-1225-3p (miR-1225-3p) and ErbB2 mRNA was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) assays. The clinical value of DANCR was checked by a ROC curve analysis, a Kaplan-Meier analysis and a Pearson Chi-Square test. Transwell chamber assays were performed to determine the migration and invasion ability changes of SPCA1 and A549 cells. The protein expression of ErbB2 was tested by Western blot assays. The targeted binding effect between miR-1225-3p and DANCR or ErbB2 was confirmed by a Dual-Luciferase reporter assay and an RNA pull-down assay, respectively.

RESULTS: In the current study, it was found that DANCR was upregulated and correlated with poor prognosis in patients with NSCLC. DANCR promoted NSCLC cells migration and invasion via upregulation of ErbB2. DANCR regulated ErbB2 at posttranscriptional level. Mechanically, it was illustrated that miR-1225-3p negatively regulated ErbbB2 and it-mediated migration and invasion via directly targeting in NSCLC cells. Meanwhile, it was showed that DANCR interacted with miR-1225-3p in a reciprocal suppression manner. Even further, through a RIP assay and a luciferase assay, we showed that DANCR interacted with miR-1225-3p through a microRNA response element (MRE-1225-3p) via directly binding. Finally, it was demonstrated that DANCR served as a miR-1225-3p sponge to promote ErbB2 expression and to facilitate ErbB2-mediated migration and invasion in NSCLC cells.

CONCLUSIONS: In the current study, it was illustrated that DNACR promoted ErbB2-mediated migration and invasion via working as a ceRNA of miR-1225-3p in NSCLC cells.

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