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RESEARCH FRONT
Contents Vol 69(10)

Therapeutic Potential of miR-494 in Thrombosis and Other Diseases: A Review

Jasmine Tay A B C , Jim Tiao A B , Quintin Hughes A , Grace Gilmore B and Ross Baker A B
+ Author Affiliations
- Author Affiliations

A Western Australian Centre for Thrombosis and Haemostasis, Murdoch University, Building 390, Discovery Way, Murdoch, WA 6150, Australia.

B Perth Blood Institute, Hollywood Specialist Centre, Lower Ground Floor, 3/95 Monash Avenue, Nedlands, WA 6009, Australia.

C Corresponding author. Email: j.tay@wacth.org




Dr Jasmine Tay is a Postdoctoral Scientist and the co-recipient of the Caruso Family Postdoctoral Research Fellowship at the West Australian Centre for Thrombosis and Haemophilia located in Murdoch University. She received her Ph.D. from the UWA School of Pathology and Laboratory Medicine in 2013, where she investigated the efficacy of androgens in the treatment of poor prognosis breast tumours. Jasmine has continued to pursue her interest in steroid hormone signalling in disease and joined Professor Ross Baker’s laboratory to study oestrogen-regulated microRNAs associated with venous thrombosis during pregnancy and the role of circulating miRNAs in regulating haemostasis.


Dr Jim Tiao received his B.Sc. (first class honours) and Ph.D. from the University of Western Australia. After earning his postgraduate degree, he undertook post-doctoral training in Professor Bettler’s laboratory at the Biozentrum-Pharmazentrum in Basel, Switzerland, where he made contributions towards the understanding of the novel GABAB receptor function. Dr Tiao returned to Perth in 2009 as a senior scientist at GeneStream Pty Ltd where he developed, and patented, novel luciferase-based molecular tools currently marketed by ThermoFisher Scientific. His research interests at WACTH Murdoch University includes developing novel assays for measuring ADAMTS13 and related proteins in microangiopathic thrombocytopenia patients.


Dr Quintin Hughes is a Caruso Family Postdoctoral Fellow and a lecturer working at the Western Australian Centre for Thrombosis and Haemostasis, based at Murdoch University in Western Australia. Completing his Ph.D. in 2009, Quintin went on to become the senior medical scientist in the Molecular Haematology Department at Royal Perth Hospital, assisting in the diagnosis and monitoring of haematological malignancies and working in transfusion medicine and bone marrow transplants to provide patient-specific molecular-based information. His research interests include hormonal regulation of the haemostatic system, including microRNA and transcriptional regulation of haemostatic genes.


Ms Grace Gilmore is a research scientist at the Perth Blood Institute with over 20 years of experience in specialist diagnostic coagulation testing. She completed a bachelor of applied science in medical technology at the WA Institute of Technology, and went on to complete a post-graduate diploma in haematology in 1986. Ms Gilmore’s current research involves clinical trials investigating the efficacy, pharmacokinetics and reversal of direct oral anticoagulants such as rivaroxaban and apixaban. Ms Gilmore is also the senior medical scientist at WACTH Murdoch University.


Professor Ross I. Baker is the director of WACTH Murdoch University. As Principal Investigator in more than 85 large international phase II and III clinical trials, he has actively led and participated in clinical research in venous thromboembolism, stroke, haemophilia, thrombocytopenia, and other bleeding disorders. He has authored or co-authored over 100 papers in peer-reviewed journals and has been an invited speaker at national and international meetings on coagulation disorders. His research interest is focused on developing novel molecular regulators of coagulation factors into clinical therapies and/or biologics.

Australian Journal of Chemistry 69(10) 1078-1093 https://doi.org/10.1071/CH16020
Submitted: 15 January 2016  Accepted: 7 March 2016   Published: 7 April 2016

Abstract

Functional nucleic acids, such as microRNAs (miRNAs), have been implicated in the pathophysiology of many diseases. The miRNA expression profiles of various cancers including haematological malignancies are well defined, but the role of miRNAs in haemostasis and the regulation of coagulation is poorly understood. We identified that miR-494 is oestrogen responsive and directly targets the anticoagulant protein, Protein S, as a mechanism for acquiring Protein S deficiency under high oestrogenic conditions such as during pregnancy and oral contraceptive use. Furthermore, previous studies have also characterised miR-494 to be involved in many biological processes. This paper reviews the current knowledge in the role of miRNAs in regulating haemostatic proteins and the known biological functions of miR-494, highlighting miR-494 as an emerging therapeutic target, with an overview of the strategy we have employed in identifying functional nucleic acids such as miRNAs that target haemostatic factors and the therapeutic potential of miR-494-directed therapy for the treatment of thrombotic disorders.


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