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