The Role of Long Non-Coding RNA DANCR in Non-Small Cell Lung Cancer

Abstract

Long non-coding RNA Differentiation Antagonizing Non-protein Coding RNA (lncRNA-DANCR) has been associated with poor prognosis in multiple cancers, and has been shown to promote cancer stemness and invasion. However, the exact mechanisms by which DANCR promotes non-small cell lung cancer (NSCLC) progression remain elusive. In this study, we inhibited DANCR expression in two NSCLC cell lines, A549 and H1755, and found that DANCR knockdown (KD) impeded cell migration, decreased viability, and reduced stem-like characteristics. Wnt signaling has been shown to promote NSCLC proliferation, stemness, and invasion; therefore, we hypothesized that DANCR may regulate these activities through induction of the Wnt/β-catenin pathway. DANCR KD reduced β-catenin signaling and protein expression as well as decreased the expression of β-catenin gene targets c-Myc and Axin2. One of the well-defined functions of lncRNAs is their ability to bind and inhibit microRNAs (miRs). Through in silico analysis, we identified the tumor suppressor miR-216a as a potential binding partner to DANCR and confirmed this binding through co-immunoprecipitation and luciferase reporter assays. Furthermore, we showed that DANCR induced β-catenin protein expression, which was effectively blocked with miR-216a overexpression. Our findings illustrate a role of DANCR in NSCLC migration and stemness, and suggest a novel DANCR/miR-216a signaling axis in the Wnt/β-catenin pathway.