{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:34:19Z","timestamp":1786970059549,"version":"build-2736575974"},"reference-count":50,"publisher":"Georg Thieme Verlag KG","issue":"11","funder":[{"name":"Murdoch University Small Grants"},{"name":"Perth Blood Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Background\u2003High estradiol (E2) levels are linked to an increased risk of venous thromboembolism; however, the underlying molecular mechanism(s) remain poorly understood. We previously identified an E2-responsive microRNA (miR), miR-494\u20133p, that downregulates protein S expression, and posited additional coagulation factors, such as tissue factor, may be regulated in a similar manner via miRs.<\/jats:p><jats:p>\n          Objectives\u2003To evaluate the coagulation capacity of cohorts with high physiological E2, and to further characterize novel E2-responsive miR and miR regulation on tissue factor in E2-related hypercoagulability.<\/jats:p><jats:p>\n          Methods\u2003Ceveron Alpha thrombin generation assay (TGA) was used to assess plasma coagulation profile of three cohorts. The effect of physiological levels of E2, 10\u2009nM, on miR expression in HuH-7 cells was compared using NanoString nCounter and validated with independent assays. The effect of tissue factor-interacting miR was confirmed by dual-luciferase reporter assays, immunoblotting, flow cytometry, biochemistry assays, and TGA.<\/jats:p><jats:p>\n          Results\u2003Plasma samples from pregnant women and women on the contraceptive pill were confirmed to be hypercoagulable (compared with sex-matched controls). At equivalent and high physiological levels of E2, miR-365a-3p displayed concordant E2 downregulation in two independent miR quantification platforms, and tissue factor protein was upregulated by E2 treatment. Direct interaction between miR-365a-3p and F3-3\u2032UTR was confirmed and overexpression of miR-365a-3p led to a decrease of (1) tissue factor mRNA transcripts, (2) protein levels, (3) activity, and (4) tissue factor-initiated thrombin generation.<\/jats:p><jats:p>\n          Conclusion\u2003miR-365a-3p is a novel tissue factor regulator. High E2 concentrations induce a hypercoagulable state via a miR network specific for coagulation factors.<\/jats:p>","DOI":"10.1055\/a-1382-9983","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T03:35:48Z","timestamp":1612496148000},"page":"1483-1496","source":"Crossref","is-referenced-by-count":6,"title":["Estradiol-Responsive miR-365a-3p Interacts with Tissue Factor 3\u2032UTR to Modulate Tissue Factor-Initiated Thrombin Generation"],"prefix":"10.1055","volume":"121","author":[{"given":"Jiayin","family":"Tian","sequence":"additional","affiliation":[{"name":"Western Australian Centre for Thrombosis and Haemostasis, Murdoch University, Murdoch, Perth, Australia"},{"name":"Perth Blood Institute, West Perth, Perth, Australia"},{"name":"College of Science, Health, Engineering and Education, Murdoch University, Murdoch, Perth, Australia"},{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Health Futures Institute, Murdoch University, Murdoch, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray J.","family":"Adams","sequence":"additional","affiliation":[{"name":"College of Science, Health, Engineering and Education, Murdoch University, Murdoch, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine Wee Ting","family":"Tay","sequence":"additional","affiliation":[{"name":"Western Australian Centre for Thrombosis and Haemostasis, Murdoch University, Murdoch, Perth, Australia"},{"name":"Perth Blood Institute, West Perth, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"James","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Powell","sequence":"additional","affiliation":[{"name":"Western Australian Centre for Thrombosis and Haemostasis, Murdoch University, Murdoch, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quintin W.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Western Australian Centre for Thrombosis and Haemostasis, Murdoch University, Murdoch, Perth, Australia"},{"name":"Perth Blood Institute, West Perth, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Gilmore","sequence":"additional","affiliation":[{"name":"Western Australian Centre for Thrombosis and Haemostasis, Murdoch University, Murdoch, Perth, Australia"},{"name":"Perth Blood Institute, West Perth, Perth, Australia"},{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Health Futures Institute, Murdoch University, Murdoch, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross I.","family":"Baker","sequence":"additional","affiliation":[{"name":"Western Australian Centre for Thrombosis and Haemostasis, Murdoch University, Murdoch, Perth, Australia"},{"name":"Perth Blood Institute, West Perth, Perth, Australia"},{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Health Futures Institute, Murdoch University, Murdoch, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim Yu-Hsiang","family":"Tiao","sequence":"additional","affiliation":[{"name":"Western Australian Centre for Thrombosis and Haemostasis, Murdoch University, Murdoch, Perth, Australia"},{"name":"Perth Blood Institute, West Perth, Perth, Australia"},{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Health Futures Institute, Murdoch University, Murdoch, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"ref1","first-page":"45","article-title":"Transcriptional activation by oestrogen receptors","volume":"63","author":"M G 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