PMID- 33302540
OWN - NLM
STAT- MEDLINE
DCOM- 20210625
LR  - 20230219
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 10
IP  - 12
DP  - 2020 Dec 8
TI  - Long Noncoding RNA DANCR Activates Wnt/beta-Catenin Signaling through MiR-216a 
      Inhibition in Non-Small Cell Lung Cancer.
LID - 10.3390/biom10121646 [doi]
LID - 1646
AB  - 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/beta-catenin pathway. DANCR KD reduced beta-catenin signaling and protein 
      expression, and decreased the expression of beta-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 beta-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/beta-catenin 
      pathway.
FAU - Yu, Justine E
AU  - Yu JE
AUID- ORCID: 0000-0002-1113-1319
AD  - Program in Molecular Medicine, University of Maryland Graduate Program in Life 
      Sciences, Baltimore, MD 21201, USA.
FAU - Ju, Julia A
AU  - Ju JA
AUID- ORCID: 0000-0002-6395-4501
AD  - Marlene and Stewart Greenebaum NCI Comprehensive Cancer Center, University of 
      Maryland School of Medicine, Baltimore, MD 21201, USA.
FAU - Musacchio, Nicholas
AU  - Musacchio N
AD  - Department of Biochemistry and Molecular Biology, University of Maryland School 
      of Medicine, Baltimore, MD 21201, USA.
FAU - Mathias, Trevor J
AU  - Mathias TJ
AUID- ORCID: 0000-0002-2830-8475
AD  - Program in Molecular Medicine, University of Maryland Graduate Program in Life 
      Sciences, Baltimore, MD 21201, USA.
FAU - Vitolo, Michele I
AU  - Vitolo MI
AUID- ORCID: 0000-0001-8055-9645
AD  - Marlene and Stewart Greenebaum NCI Comprehensive Cancer Center, University of 
      Maryland School of Medicine, Baltimore, MD 21201, USA.
AD  - Department of Pharmacology, University of Maryland School of Medicine, Baltimore, 
      MD 21201, USA.
LA  - eng
GR  - T32 CA154274/CA/NCI NIH HHS/United States
GR  - RSG-18-028-01-CSM/American Cancer Society/International
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201208
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (AXIN2 protein, human)
RN  - 0 (Axin Protein)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (DANCR long noncoding RNA, human)
RN  - 0 (MIRN216 microRNA, human)
RN  - 0 (MYC protein, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (SOX2 protein, human)
RN  - 0 (SOXB1 Transcription Factors)
RN  - 0 (beta Catenin)
SB  - IM
MH  - A549 Cells
MH  - Apoptosis/genetics
MH  - Axin Protein/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Epithelial Cells/*metabolism/pathology
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - MicroRNAs/antagonists & inhibitors/*genetics/metabolism
MH  - Proto-Oncogene Proteins c-myc/genetics/metabolism
MH  - RNA, Long Noncoding/antagonists & inhibitors/*genetics/metabolism
MH  - RNA, Small Interfering/genetics/metabolism
MH  - SOXB1 Transcription Factors/genetics/metabolism
MH  - Spheroids, Cellular/metabolism/pathology
MH  - Wnt Signaling Pathway/*genetics
MH  - beta Catenin/*genetics/metabolism
PMC - PMC7764320
OTO - NOTNLM
OT  - Wnt
OT  - lncRNA
OT  - microRNA
OT  - non-small cell lung cancer
OT  - beta-catenin
COIS- The authors declare no conflict of interest.
EDAT- 2020/12/12 06:00
MHDA- 2021/06/29 06:00
PMCR- 2020/12/08
CRDT- 2020/12/11 01:01
PHST- 2020/11/17 00:00 [received]
PHST- 2020/12/06 00:00 [revised]
PHST- 2020/12/06 00:00 [accepted]
PHST- 2020/12/11 01:01 [entrez]
PHST- 2020/12/12 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2020/12/08 00:00 [pmc-release]
AID - biom10121646 [pii]
AID - biomolecules-10-01646 [pii]
AID - 10.3390/biom10121646 [doi]
PST - epublish
SO  - Biomolecules. 2020 Dec 8;10(12):1646. doi: 10.3390/biom10121646.