The role of small RNAs in Paget's associated osteosarcoma

Green, Darrell, Dalmay, Tamas and Fraser, William (2018) The role of small RNAs in Paget's associated osteosarcoma. Journal of Bone Oncology, 13. p. 54. ISSN 2212-1374

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Abstract

Small RNAs (sRNAs) are a class of non-coding RNA molecules that arekey regulators of gene expression. SRNAs are also specific biomarkersdue to their dysregulation in disease. Next generation sequencing is thegold standard for sRNA discovery, profiling and expression analysis.Bias has been found in different platforms of sequencing due to RNAligase preference for sequence complementarity between sRNA andadapters. We developed high definition (HD) adapters to overcome thebias. We applied the use of HD adapters and sequencing to our studiesof bone cancer. One of these studies investigated sRNA expression inPaget’s associated osteosarcoma, a rare complication of Paget’s diseaseof bone that carries a poor prognosis. We found that expression of amicroRNA, miR-16, was highly expressed in Paget’s associated osteo-sarcoma tissue when compared to controls and Paget’s disease of bone.Bioinformatics analysis revealed miR-16 directly targets the sequesto-some 1 (SQSTM1) messenger RNA. SQSTM1 protein has long been as-sociated with Paget’s disease of bone development. SQSTM1 was hy-pothesised to be involved with transformation to osteosarcoma asSQSTM1 variants are positively associated with disease severity. Wespeculated that negative regulation of SQSTM1 by miR-16 incapacitatesSQSTM1’s role in the Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor erythroid 2-like 2 (NFE2L2) pathway, a major cellulardefence mechanism against oxidative stress and cancer development.Molecular testing may help provide a robust diagnosis and is particu-larly useful in rare cancers such as Paget’s associated osteosarcomawhere transformation is often missed until late stage. We are now in-vestigating this biological data further, using single cell simultaneousgenome and transcriptome sequencing.

Item Type: Article
Additional Information: Abstract written by Dr Stephen Tuck chair of the writing group on behalf of: Stuart H Ralston, Luis Corral-Gudino, Cyrus Cooper, Roger M Francis, William D Fraser, Luigi Gennari, Nuria Guanabens, M Kassim Javaid, Robert Layfield, Terence W O’Neill, R Graham G Russell,Michael D Stone, Keith Simpson, Diana Wilkinson, Ruth Wills, Carola Zillikens, and Stephen P Tuck.
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
Depositing User: LivePure Connector
Date Deposited: 26 Oct 2018 12:30
Last Modified: 22 Jul 2020 02:38
URI: https://ueaeprints.uea.ac.uk/id/eprint/68651
DOI:

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