Machine learning workflows identify a microRNA signature of insulin transcription in human tissues.

Autor:	Wong WKM; Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Narellan Road & Gilchrist Drive, Campbelltown, NSW 2560, Australia.; Diabetes and Islet Biology group, Faculty of Medicine and Health, University of Sydney, 92-94 Parramatta Road, Camperdown, NSW 2050, Australia., Joglekar MV; Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Narellan Road & Gilchrist Drive, Campbelltown, NSW 2560, Australia.; Diabetes and Islet Biology group, Faculty of Medicine and Health, University of Sydney, 92-94 Parramatta Road, Camperdown, NSW 2050, Australia., Saini V; Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Narellan Road & Gilchrist Drive, Campbelltown, NSW 2560, Australia.; School of Life Sciences and the Centre for Health Technologies, University of Technology Sydney, 15 Broadway, Ultimo, NSW 2007, Australia., Jiang G; Department of Medicine and Therapeutics, and Hong Kong Institute of Diabetes and Obesity, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Special Administrative Region, China., Dong CX; Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Narellan Road & Gilchrist Drive, Campbelltown, NSW 2560, Australia.; Diabetes and Islet Biology group, Faculty of Medicine and Health, University of Sydney, 92-94 Parramatta Road, Camperdown, NSW 2050, Australia., Chaitarvornkit A; Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Narellan Road & Gilchrist Drive, Campbelltown, NSW 2560, Australia.; Diabetes and Islet Biology group, Faculty of Medicine and Health, University of Sydney, 92-94 Parramatta Road, Camperdown, NSW 2050, Australia., Maciag GJ; Department of Science and Environment, Roskilde University, Universitetsvej 1, 4000 Roskilde, Denmark., Gerace D; School of Life Sciences and the Centre for Health Technologies, University of Technology Sydney, 15 Broadway, Ultimo, NSW 2007, Australia., Farr RJ; Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Narellan Road & Gilchrist Drive, Campbelltown, NSW 2560, Australia.; Diabetes and Islet Biology group, Faculty of Medicine and Health, University of Sydney, 92-94 Parramatta Road, Camperdown, NSW 2050, Australia., Satoor SN; Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Narellan Road & Gilchrist Drive, Campbelltown, NSW 2560, Australia.; Diabetes and Islet Biology group, Faculty of Medicine and Health, University of Sydney, 92-94 Parramatta Road, Camperdown, NSW 2050, Australia., Sahu S; Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Narellan Road & Gilchrist Drive, Campbelltown, NSW 2560, Australia.; Diabetes and Islet Biology group, Faculty of Medicine and Health, University of Sydney, 92-94 Parramatta Road, Camperdown, NSW 2050, Australia., Sharangdhar T; Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Narellan Road & Gilchrist Drive, Campbelltown, NSW 2560, Australia.; Diabetes and Islet Biology group, Faculty of Medicine and Health, University of Sydney, 92-94 Parramatta Road, Camperdown, NSW 2050, Australia., Ahmed AS; Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Narellan Road & Gilchrist Drive, Campbelltown, NSW 2560, Australia.; Diabetes and Islet Biology group, Faculty of Medicine and Health, University of Sydney, 92-94 Parramatta Road, Camperdown, NSW 2050, Australia., Chew YV; Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, 176 Hawkesbury Road, Westmead, NSW 2145, Australia., Liuwantara D; Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, 176 Hawkesbury Road, Westmead, NSW 2145, Australia., Heng B; Faculty of Medicine Health and Human Sciences, Macquarie University, Sydney, NSW 2019, Australia., Lim CK; Faculty of Medicine Health and Human Sciences, Macquarie University, Sydney, NSW 2019, Australia., Hunter J; Centre for the Endothelium, Vascular Biology Program, Centenary Institute, University of Sydney Medical School, Locked Bag #6, Newtown, NSW 2042, Australia., Januszewski AS; NHMRC Clinical Trials Centre, University of Sydney, 92-94 Parramatta Road, Camperdown, NSW 2050, Australia., Sørensen AE; Department of Science and Environment, Roskilde University, Universitetsvej 1, 4000 Roskilde, Denmark., Akil ASA; Department of Human Genetics-Precision Medicine Program, Sidra Medicine, P.O. Box 26999, Doha, Qatar., Gamble JR; Centre for the Endothelium, Vascular Biology Program, Centenary Institute, University of Sydney Medical School, Locked Bag #6, Newtown, NSW 2042, Australia., Loudovaris T; St Vincent's Institute and The University of Melbourne Department of Medicine, 9 Princes Street, Fitzroy, VIC, Australia., Kay TW; St Vincent's Institute and The University of Melbourne Department of Medicine, 9 Princes Street, Fitzroy, VIC, Australia., Thomas HE; St Vincent's Institute and The University of Melbourne Department of Medicine, 9 Princes Street, Fitzroy, VIC, Australia., O'Connell PJ; Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, 176 Hawkesbury Road, Westmead, NSW 2145, Australia., Guillemin GJ; Faculty of Medicine Health and Human Sciences, Macquarie University, Sydney, NSW 2019, Australia., Martin D; Upper GI Surgery, Strathfield Hospital, 2/3 Everton Road, Strathfield, NSW 2135, Australia., Simpson AM; School of Life Sciences and the Centre for Health Technologies, University of Technology Sydney, 15 Broadway, Ultimo, NSW 2007, Australia., Hawthorne WJ; Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, 176 Hawkesbury Road, Westmead, NSW 2145, Australia., Dalgaard LT; Department of Science and Environment, Roskilde University, Universitetsvej 1, 4000 Roskilde, Denmark., Ma RCW; Department of Medicine and Therapeutics, and Hong Kong Institute of Diabetes and Obesity, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Special Administrative Region, China., Hardikar AA; Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Narellan Road & Gilchrist Drive, Campbelltown, NSW 2560, Australia.; Diabetes and Islet Biology group, Faculty of Medicine and Health, University of Sydney, 92-94 Parramatta Road, Camperdown, NSW 2050, Australia.; Department of Science and Environment, Roskilde University, Universitetsvej 1, 4000 Roskilde, Denmark.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2021 Mar 31; Vol. 24 (4), pp. 102379. Date of Electronic Publication: 2021 Mar 31 (Print Publication: 2021).
DOI:	10.1016/j.isci.2021.102379
Abstrakt:	Dicer knockout mouse models demonstrated a key role for microRNAs in pancreatic β-cell function. Studies to identify specific microRNA(s) associated with human (pro-)endocrine gene expression are needed. We profiled microRNAs and key pancreatic genes in 353 human tissue samples. Machine learning workflows identified microRNAs associated with (pro-)insulin transcripts in a discovery set of islets (n = 30) and insulin-negative tissues (n = 62). This microRNA signature was validated in remaining 261 tissues that include nine islet samples from individuals with type 2 diabetes. Top eight microRNAs (miR-183-5p, -375-3p, 216b-5p, 183-3p, -7-5p, -217-5p, -7-2-3p, and -429-3p) were confirmed to be associated with and predictive of (pro-)insulin transcript levels. Use of doxycycline-inducible microRNA-overexpressing human pancreatic duct cell lines confirmed the regulatory roles of these microRNAs in (pro-)endocrine gene expression. Knockdown of these microRNAs in human islet cells reduced (pro-)insulin transcript abundance. Our data provide specific microRNAs to further study microRNA-mRNA interactions in regulating insulin transcription. Competing Interests: A patent application (WO2019000017A1) was filed. (© 2021 The Authors.)
Databáze:	MEDLINE
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