MicroRNA expression in a phosphaturic mesenchymal tumour

Green, Darrell ORCID: https://orcid.org/0000-0002-0217-3322, Mohorianu, Irina, Piec, Isabelle ORCID: https://orcid.org/0000-0002-0648-1330, Turner, Jeremy, Beadsmoore, Clare, Toms, Andoni, Ball, Richard, Nolan, John, McNamara, Iain, Dalmay, Tamas ORCID: https://orcid.org/0000-0003-1492-5429 and Fraser, William D (2017) MicroRNA expression in a phosphaturic mesenchymal tumour. Bone Reports, 7. 63–69. ISSN 2352-1872

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Phosphaturic mesenchymal tumours are a heterogeneous set of bone and soft tissue neoplasms that can cause a number of paraneoplastic syndromes such as tumour induced osteomalacia. The term phosphaturic comes from the common finding that these tumours secrete high levels of fibroblast growth factor 23 which causes renal phosphate wasting leading to hypophosphatemia. Phosphaturic mesenchymal tumours are rare and diagnosis is difficult. A very active 68 year old male presented with bone pain and muscle weakness. He was hypophosphataemic and total alkaline phosphatase was markedly elevated. The patient was placed on vitamin D supplementation but his condition progressed. In the fifth year of presentation the patient required the use of a wheelchair and described “explosive” bone pain on physical contact. Serum 1,25 dihydroxyvitamin D was low and serum fibroblast growth factor 23 was significantly elevated, raising suspicion of a phosphaturic mesenchymal tumour. A lesion was detected in his left femoral head and the patient underwent a total hip replacement. The patient displayed a rapid improvement to his condition and during a three year follow up period he returned to an active lifestyle. As molecular testing may help provide a robust diagnosis and is particularly useful in rare diseases we took a next generation sequencing approach to identify a differential expression of small RNAs in the resected tumour. Small RNAs are non-coding RNA molecules that play a key role in regulation of gene expression and can be used as specific biomarkers. We found an upregulation of miR-197. We also found a downregulation of miR-20b, miR-144 and miR-335 which is a small RNA profile typical of osteosarcoma. MiR-21, the most frequently upregulated microRNA in cancer, was downregulated. We conclude that the specific small RNA profile is typical of osteosarcoma except for the downregulation of oncogenic miR-21. Transcriptional plasticity of miR-197, which is computationally predicted to target fibroblast growth factor 23 messenger RNA, may be upregulated in a cellular effort to correct the ectopic expression of the protein.

Item Type: Article
Uncontrolled Keywords: fgf23,hypophosphatemia,tumour,microrna,next generation sequencing,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Computing Sciences
Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Science > Research Groups > Plant Sciences
Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User: Pure Connector
Date Deposited: 09 Sep 2017 05:06
Last Modified: 19 Oct 2023 02:03
URI: https://ueaeprints.uea.ac.uk/id/eprint/64782
DOI: 10.1016/j.bonr.2017.09.001


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