Cargando…
Long Noncoding RNA DANCR Activates Wnt/β-Catenin Signaling through MiR-216a Inhibition in Non-Small Cell Lung Cancer
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 stud...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764320/ https://www.ncbi.nlm.nih.gov/pubmed/33302540 http://dx.doi.org/10.3390/biom10121646 |
_version_ | 1783628228788748288 |
---|---|
author | Yu, Justine E. Ju, Julia A. Musacchio, Nicholas Mathias, Trevor J. Vitolo, Michele I. |
author_facet | Yu, Justine E. Ju, Julia A. Musacchio, Nicholas Mathias, Trevor J. Vitolo, Michele I. |
author_sort | Yu, Justine E. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7764320 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77643202020-12-27 Long Noncoding RNA DANCR Activates Wnt/β-Catenin Signaling through MiR-216a Inhibition in Non-Small Cell Lung Cancer Yu, Justine E. Ju, Julia A. Musacchio, Nicholas Mathias, Trevor J. Vitolo, Michele I. Biomolecules Article 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. MDPI 2020-12-08 /pmc/articles/PMC7764320/ /pubmed/33302540 http://dx.doi.org/10.3390/biom10121646 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yu, Justine E. Ju, Julia A. Musacchio, Nicholas Mathias, Trevor J. Vitolo, Michele I. Long Noncoding RNA DANCR Activates Wnt/β-Catenin Signaling through MiR-216a Inhibition in Non-Small Cell Lung Cancer |
title | Long Noncoding RNA DANCR Activates Wnt/β-Catenin Signaling through MiR-216a Inhibition in Non-Small Cell Lung Cancer |
title_full | Long Noncoding RNA DANCR Activates Wnt/β-Catenin Signaling through MiR-216a Inhibition in Non-Small Cell Lung Cancer |
title_fullStr | Long Noncoding RNA DANCR Activates Wnt/β-Catenin Signaling through MiR-216a Inhibition in Non-Small Cell Lung Cancer |
title_full_unstemmed | Long Noncoding RNA DANCR Activates Wnt/β-Catenin Signaling through MiR-216a Inhibition in Non-Small Cell Lung Cancer |
title_short | Long Noncoding RNA DANCR Activates Wnt/β-Catenin Signaling through MiR-216a Inhibition in Non-Small Cell Lung Cancer |
title_sort | long noncoding rna dancr activates wnt/β-catenin signaling through mir-216a inhibition in non-small cell lung cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764320/ https://www.ncbi.nlm.nih.gov/pubmed/33302540 http://dx.doi.org/10.3390/biom10121646 |
work_keys_str_mv | AT yujustinee longnoncodingrnadancractivateswntbcateninsignalingthroughmir216ainhibitioninnonsmallcelllungcancer AT jujuliaa longnoncodingrnadancractivateswntbcateninsignalingthroughmir216ainhibitioninnonsmallcelllungcancer AT musacchionicholas longnoncodingrnadancractivateswntbcateninsignalingthroughmir216ainhibitioninnonsmallcelllungcancer AT mathiastrevorj longnoncodingrnadancractivateswntbcateninsignalingthroughmir216ainhibitioninnonsmallcelllungcancer AT vitolomichelei longnoncodingrnadancractivateswntbcateninsignalingthroughmir216ainhibitioninnonsmallcelllungcancer |