Adams, M

Boissinot, M

Bond, J

Higgins, J

King, H

Lawler, SE

Short, SC

Steele, LP

Tomlinson, DC

Wurdak, H

Neuro-Oncology

M. Boissinot

H. King

M. Adams

J. Higgins

L. P. Steele

H. Wurdak

J. Bond

D. C. Tomlinson

S. E. Lawler

S. C. Short

Crossref

P01.01 Ectopic expression of microRNA-1300 in adult and paediatric glioma cells induces cytokinesis failure and apoptosis via ECT2

White Rose Research Online

This is a repository copy of Ectopic expression of microRNA-1300 in adult and paediatric glioma cells induces cytokinesis failure and apoptosis via ECT2.White Rose Research Online URL for this paper:http://eprints.whiterose.ac.uk/111135/Version: Accepted VersionProceedings Paper:Boissinot, M, King, H, Adams, M et al. (7 more authors) (2016) Ectopic expression of microRNA-1300 in adult and paediatric glioma cells induces cytokinesis failure and apoptosis via ECT2. In: Neuro-Oncology. 12th Meeting of the European Association of Neuro-Oncology, 12-16 Oct 2016, Mannheim/Heidelberg, Germany. Oxford University Press , iv18-iv18. https://doi.org/10.1093/neuonc/now188.058© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. This is a pre-copyedited, author-produced PDF of an article accepted for publication in Neuro-Oncology following peer review. The version of record: M. Boissinot, H. King, M. Adams, J. Higgins, L. P. Steele, H. Wurdak, J. Bond, D. C. Tomlinson, S. E. Lawler, and S. C. Short (2016) P01.01 Ectopic expression of microRNA-1300 in adult and paediatric glioma cells induces cytokinesis failure and apoptosis via ECT2, Neuro-Oncology, 18 (suppl 4), p. iv18. doi:10.1093/neuonc/now188.058 is available online at: https://doi.org/10.1093/neuonc/now188.058. Uploaded in accordance with the publisher's self-archiving policy.eprints@whiterose.ac.ukhttps://eprints.whiterose.ac.uk/Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version - refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher’s website. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. P01.01 ECTOPIC EXPRESSION OF MICRORNA-1300 IN ADULT  AND PAEDIATRIC GLIOMA CELLS INDUCES CYTOKINESIS  FAILURE AND APOPTOSIS VIA ECT2  M. Boissinot, H. King, M. Adams, J. Higgins, L. P. Steele, H. Wurdak, J. Bond, D. C. Tomlinson, S. E. Lawler, S. C. Short  MicroRNAs are proving to be potent tumour suppressors in cancer. Many microRNAs are in pre-clinical and clinical validation. A high-throughput screen was performed to identify microRNAs with potent anti-proliferative and/or pro-apoptotic effect in a panel of glioma cell lines. MicroRNA-1300 was identified as a potent pro-apoptotic candidate. Its effect was validated in U251 (adult) and KNS42 (paediatric) established cell lines as well as two newly established patient-derived glioma stem-like cell lines. Initial validation showed that microRNA-1300 is not usually expressed in glioma and that ectopic expression of a mimic of its mature form leads to cytokinesis failure followed by apoptosis. Further characterization indicated that this effect is mediated through its target ECT2, a GTP exchange factor responsible for the recruitment of RhoA at the cleavage furrow in mitosis. In addition, we confirmed that normal cells surrounding the tumour are not affected by the expression of microRNA-1300 in a model of quiescent brain cells, thus excluding off-target cytotoxicity. Investigation of the physiological interaction and role of microRNA-1300 and ECT2 showed that the expression of microRNA-1300 is normally restricted to megakaryopoiesis, during endomitosis, to allow for the formation of plurinuclear megakaryoblasts. This is consistent with the effect we observed on ectopic expression of microRNA-1300 in which glioma cells become binucleated following cell cycle arrest and apoptosis ensues. In conclusion, microRNA-1300 was identified as a potent, cytotoxic microRNA with potential therapeutic effect in glioblastoma. Ectopic expression of a microRNA in an abnormal cellular context is a novel approach to microRNA therapeutics. Research is ongoing, aiming to optimise the use of microRNA-1300 in a pre-clinical setting and to assess its in vivo cytotoxicity alone and in combination with radiation. 