Long Noncoding RNA DANCR Activates Wnt/β-Catenin Signaling through MiR-216a Inhibition in Non-Small Cell Lung Cancer

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2020-12, Vol.10 (12), p.1646
• Main Authors: Yu, Justine E, Ju, Julia A, Musacchio, Nicholas, Mathias, Trevor J, Vitolo, Michele I
• Format: Article
• Language: English
• Subjects: A549 Cells; Apoptosis - genetics; Axin Protein - genetics; Axin Protein - metabolism; beta Catenin - genetics; beta Catenin - metabolism; c-Myc protein; Cell differentiation; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Epithelial Cells - metabolism; Epithelial Cells - pathology; Gene expression; Gene Expression Regulation, Neoplastic; Genomes; Humans; Kinases; lncRNA; Lung cancer; Metastasis; microRNA; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Myc protein; non-small cell lung cancer; Non-small cell lung carcinoma; Proteins; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; RNA, Long Noncoding - antagonists & inhibitors; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Signal transduction; Small cell lung carcinoma; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - metabolism; Spheroids, Cellular - metabolism; Spheroids, Cellular - pathology; Stem cells; Tumor suppressor genes; Tumorigenesis; Wnt; Wnt protein; Wnt Signaling Pathway - genetics; β-Catenin
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom10121646

Long noncoding RNA differentiation antagonizing nonprotein coding RNA (lncRNA-DANCR) is associated with poor prognosis in multiple cancers, and promotes cancer stemness and invasion. However, the exact mechanisms by which DANCR promotes non-small cell lung cancer (NSCLC) remain elusive. In this study, we determined that DANCR knockdown (KD) impeded cell migration and reduced stem-like characteristics in two NSCLC cell lines, A549 and H1755. Wnt signaling was 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, and 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. Through in silico analysis, we identified tumor suppressor miR-216a as a potential binding partner to DANCR, and confirmed this binding through coimmunoprecipitation and luciferase-reporter assays. Furthermore, we show that DANCR-induced β-catenin protein expression may be 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.