Journal article
Micro-Ribonucleic Acid 494 regulation of protein S expression
Journal of Thrombosis and Haemostasis, Vol.11(8), pp.1547-1555
2013
Abstract
BACKGROUND:
Acquired protein S (PS) deficiency is highly associated with elevated circulating estrogen levels resulting from pregnancy, oral contraceptives, and estrogen replacement therapy; however, the mechanism of estrogen-mediated acquired PS deficiency remains poorly understood. Increasing evidence indicates that estrogen receptor signaling can indirectly modulate the expression of target genes at the post-transcriptional level by modulating the expression of microRNAs (miRNAs), and miRNAs have also been demonstrated to be involved in the regulation of hemostasis.
OBJECTIVES:
To investigate the mechanism of estrogen-mediated downregulation of PROS1 expression by the microRNA miR-494.
METHODS:
Computational analyses of the PROS1 3'-untranslated region (UTR) were performed to identify putative miRNA-binding sites, and direct targeting of the PROS1 3'-UTR by miR-494 was determined with dual luciferase reporter assays in HuH-7 cells. Reporter vectors containing the PROS1 3'-UTR sequence with deleted miR-494-binding sites were also analyzed with luciferase reporter assays. The effects of estrogen on miR-494 and PROS1 mRNA levels in HuH-7 cells were determined by quantitative real-time PCR, and estrogen-mediated changes to secreted PS levels in culture supernatant of HuH-7 cells were measured with an ELISA.
RESULTS:
The PROS1 3'-UTR sequence contains three putative miR-494-binding sites. miR-494 directly targets PROS1, and miR-494 levels are upregulated following estrogen treatment in HuH-7 liver cells in association with downregulated PROS1 mRNA and PS levels.
CONCLUSIONS:
The results from this study provide the first evidence for miRNA downregulation of PROS1 by miR-494, and suggest that miR-494 is involved in the mechanism of estrogen-mediated downregulation of PS expression.
Details
- Title
- Micro-Ribonucleic Acid 494 regulation of protein S expression
- Authors/Creators
- J.W. Tay (Author/Creator) - Royal Perth HospitalG. Romeo (Author/Creator) - Royal Perth HospitalQ.W. Hughes (Author/Creator) - Murdoch UniversityR.I. Baker (Author/Creator)
- Publication Details
- Journal of Thrombosis and Haemostasis, Vol.11(8), pp.1547-1555
- Publisher
- Wiley-Blackwell
- Identifiers
- 991005541561007891
- Copyright
- © 2013 International Society on Thrombosis and Haemostasis
- Murdoch Affiliation
- Centre for Haemophilia and Thrombosis Research
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
23 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.196 Micro & Long Noncoding RNA
- 1.196.68 MicroRNA in Cancer
- Web Of Science research areas
- Hematology
- Peripheral Vascular Disease
- ESI research areas
- Clinical Medicine