The role of small RNAs in Paget's associated osteosarcoma

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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.
Original languageEnglish
Pages (from-to)54
JournalJournal of Bone Oncology
Volume13
Publication statusPublished - 30 Sep 2018
Event8th International Workshop on Advances in the Molecular Pharmacology and Therapeutics of Bone and other Musculoskeletal Diseases and Cancer and Bone Society 2018 Meeting - Oxford, United Kingdom
Duration: 30 Jun 20183 Jul 2018

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