eprintid: 10094643
rev_number: 26
eprint_status: archive
userid: 608
dir: disk0/10/09/46/43
datestamp: 2020-04-08 09:33:46
lastmod: 2021-12-13 02:02:56
status_changed: 2020-04-08 09:33:46
type: article
metadata_visibility: show
creators_name: Maeshima, R
creators_name: Moulding, D
creators_name: Stoker, AW
creators_name: Hart, SL
title: MYCN Silencing by RNA Interference Induces Neurogenesis and Suppresses Proliferation in Models of Neuroblastoma with Resistance to Retinoic Acid
ispublished: pub
divisions: UCL
divisions: B02
divisions: D13
divisions: G22
divisions: G23
keywords: MYCN, neuroblastoma, retinoic acid treatment, siRNA
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
abstract: Neuroblastoma (NB) is the most common solid tumor in childhood. Twenty percent of patients display MYCN amplification, which indicates a very poor prognosis. MYCN is a highly specific target for an NB tumor therapy as MYCN expression is absent or very low in most normal cells, while, as a transcription factor, it regulates many essential cell activities in tumor cells. We aim to develop a therapy for NB based on MYCN silencing by short interfering RNA (siRNA) molecules, which can silence target genes by RNA interference (RNAi), a naturally occurring method of gene silencing. It has been shown previously that MYCN silencing can induce apoptosis and differentiation in MYCN amplified NB. In this article, we have demonstrated that siRNA-mediated silencing of MYCN in MYCN-amplified NB cells induced neurogenesis in NB cells, whereas retinoic acid (RA) treatment did not. RA can differentiate NB cells and is used for treatment of residual disease after surgery or chemotherapy, but resistance can develop. In addition, MYCN siRNA treatment suppressed growth in a MYCN-amplified NB cell line more than that by RA. Our result suggests that gene therapy using RNAi targeting MYCN can be a novel therapy toward MYCN-amplified NB that have complete or partial resistance toward RA.
date: 2020-08-06
date_type: published
official_url: https://doi.org/10.1089/nat.2019.0831
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1775517
doi: 10.1089/nat.2019.0831
lyricists_name: Hart, Stephen
lyricists_name: Maeshima, Ruhina
lyricists_name: Moulding, Dale
lyricists_name: Stoker, Andrew
lyricists_id: SLHAR52
lyricists_id: RMAES23
lyricists_id: DAMOU35
lyricists_id: AWSTO81
actors_name: Hart, Stephen
actors_id: SLHAR52
actors_role: owner
full_text_status: public
publication: Nucleic Acid Therapeutics
volume: 30
number: 4
pagerange: 237-248
event_location: United States
citation:        Maeshima, R;    Moulding, D;    Stoker, AW;    Hart, SL;      (2020)    MYCN Silencing by RNA Interference Induces Neurogenesis and Suppresses Proliferation in Models of Neuroblastoma with Resistance to Retinoic Acid.                   Nucleic Acid Therapeutics , 30  (4)   pp. 237-248.    10.1089/nat.2019.0831 <https://doi.org/10.1089/nat.2019.0831>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10094643/3/Hart_MYCN%20Silencing%20by%20RNA%20Interference%20Induces%20Neurogenesis%20and%20Suppresses%20Proliferation%20in%20Models%20of%20Neuroblastoma%20with%20Resistance%20to%20Retinoic%20Acid_AAM.pdf