Journal article
miR-99b-5p, miR-380-3p, and miR-485-3p are novel chemosensitizing miRNAs in high-risk neuroblastoma
H Holliday, J Yang, E Dodson, I Nikolic, A Kamili, M Wheatley, N Deng, S Alexandrou, TP Davis, M Kavallaris, CE Caldon, J McCarroll, K De Preter, P Mestdagh, GM Marshall, KJ Simpson, J Fletcher, A Swarbrick
Molecular Therapy | Published : 2022
Abstract
Neuroblastoma is a deadly childhood cancer arising in the developing sympathetic nervous system. High-risk patients are currently treated with intensive chemotherapy, which is curative in only 50% of children and leaves some surviving patients with life-long side effects. microRNAs (miRNAs) are critical regulators of neural crest development and are deregulated during neuroblastoma tumorigenesis, making miRNA-based drugs an attractive therapeutic avenue. A functional screen of >1,200 miRNA mimics was conducted in neuroblastoma cell lines to discover miRNAs that sensitized cells to low doses (30% inhibitory concentration [IC30]) of doxorubicin and vincristine chemotherapy used in the treatmen..
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Awarded by Ross Trust
Funding Acknowledgements
H.H, E.D., and A.S were supported by The Kids' Cancer Project, Deborah and John McMurtrie, and The Ross Trust. The Victorian Center for Functional Genomics (K.J.S. and I.N.) is funded by the Australian Cancer Research Foundation (ACRF), Phenomics Australia (PA) through funding from the Australian Government's National Collaborative Research Infrastructure Strategy (NCRIS) program, and the Peter MacCallum Cancer Centre Foundation. This work was supported by the Children's Cancer Institute, which is affiliated with the University of New South Wales (UNSW Sydney), and the Sydney Children's Hospital Network, by grants from the National Health and Medical Research (Program Grant APP1091261, Senior Research Fellowship APP1161216 to A.S., APP1144113 for J.M., and Principal Research Fellowship APP1119152 to M.K.), and by a Cancer Institute New South Wales Program grant (TPG2037 to M.K.). M.K and T.P.D. are supported by the Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology (CE140100036). Aspects of this work were funded through Cancer Australia/Kids Cancer Project (APP1184840, J.M., T.P.D., M.K.) and the Olivia Lambert Foundation (J.M.). The authors thank the Sydney Children's Tumor Bank Network (Children's Cancer Institute Tumor Bank) for providing samples and related clinical information for this study and the Children's Cancer Institute Animal Facility for providing support to this study. The authors would also like to acknowledge the Ramaciotti Center for Genomics, the Garvan Histopathology facility, and the Neuroblastoma Research Consortium (NRC) for sharing the miRNA and copy-number data. The graphical abstract was created with BioRender.com.