iScience (Apr 2021)
Machine learning workflows identify a microRNA signature of insulin transcription in human tissues
- Wilson K.M. Wong,
- Mugdha V. Joglekar,
- Vijit Saini,
- Guozhi Jiang,
- Charlotte X. Dong,
- Alissa Chaitarvornkit,
- Grzegorz J. Maciag,
- Dario Gerace,
- Ryan J. Farr,
- Sarang N. Satoor,
- Subhshri Sahu,
- Tejaswini Sharangdhar,
- Asma S. Ahmed,
- Yi Vee Chew,
- David Liuwantara,
- Benjamin Heng,
- Chai K. Lim,
- Julie Hunter,
- Andrzej S. Januszewski,
- Anja E. Sørensen,
- Ammira S.A. Akil,
- Jennifer R. Gamble,
- Thomas Loudovaris,
- Thomas W. Kay,
- Helen E. Thomas,
- Philip J. O'Connell,
- Gilles J. Guillemin,
- David Martin,
- Ann M. Simpson,
- Wayne J. Hawthorne,
- Louise T. Dalgaard,
- Ronald C.W. Ma,
- Anandwardhan A. Hardikar
Affiliations
- Wilson K.M. Wong
- 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
- Mugdha V. Joglekar
- 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
- Vijit Saini
- 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
- Guozhi Jiang
- 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
- Charlotte X. Dong
- 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
- Alissa Chaitarvornkit
- 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
- Grzegorz J. Maciag
- Department of Science and Environment, Roskilde University, Universitetsvej 1, 4000 Roskilde, Denmark
- Dario Gerace
- School of Life Sciences and the Centre for Health Technologies, University of Technology Sydney, 15 Broadway, Ultimo, NSW 2007, Australia
- Ryan J. Farr
- 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
- Sarang N. Satoor
- 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
- Subhshri Sahu
- 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
- Tejaswini Sharangdhar
- 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
- Asma S. Ahmed
- 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
- Yi Vee Chew
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, 176 Hawkesbury Road, Westmead, NSW 2145, Australia
- David Liuwantara
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, 176 Hawkesbury Road, Westmead, NSW 2145, Australia
- Benjamin Heng
- Faculty of Medicine Health and Human Sciences, Macquarie University, Sydney, NSW 2019, Australia
- Chai K. Lim
- Faculty of Medicine Health and Human Sciences, Macquarie University, Sydney, NSW 2019, Australia
- Julie Hunter
- Centre for the Endothelium, Vascular Biology Program, Centenary Institute, University of Sydney Medical School, Locked Bag #6, Newtown, NSW 2042, Australia
- Andrzej S. Januszewski
- NHMRC Clinical Trials Centre, University of Sydney, 92-94 Parramatta Road, Camperdown, NSW 2050, Australia
- Anja E. Sørensen
- Department of Science and Environment, Roskilde University, Universitetsvej 1, 4000 Roskilde, Denmark
- Ammira S.A. Akil
- Department of Human Genetics-Precision Medicine Program, Sidra Medicine, P.O. Box 26999, Doha, Qatar
- Jennifer R. Gamble
- Centre for the Endothelium, Vascular Biology Program, Centenary Institute, University of Sydney Medical School, Locked Bag #6, Newtown, NSW 2042, Australia
- Thomas Loudovaris
- St Vincent's Institute and The University of Melbourne Department of Medicine, 9 Princes Street, Fitzroy, VIC, Australia
- Thomas W. Kay
- St Vincent's Institute and The University of Melbourne Department of Medicine, 9 Princes Street, Fitzroy, VIC, Australia
- Helen E. Thomas
- St Vincent's Institute and The University of Melbourne Department of Medicine, 9 Princes Street, Fitzroy, VIC, Australia
- Philip J. O'Connell
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, 176 Hawkesbury Road, Westmead, NSW 2145, Australia
- Gilles J. Guillemin
- Faculty of Medicine Health and Human Sciences, Macquarie University, Sydney, NSW 2019, Australia
- David Martin
- Upper GI Surgery, Strathfield Hospital, 2/3 Everton Road, Strathfield, NSW 2135, Australia
- Ann M. Simpson
- School of Life Sciences and the Centre for Health Technologies, University of Technology Sydney, 15 Broadway, Ultimo, NSW 2007, Australia
- Wayne J. Hawthorne
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, 176 Hawkesbury Road, Westmead, NSW 2145, Australia
- Louise T. Dalgaard
- Department of Science and Environment, Roskilde University, Universitetsvej 1, 4000 Roskilde, Denmark
- Ronald C.W. Ma
- 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
- Anandwardhan A. Hardikar
- 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; Corresponding author
- Journal volume & issue
-
Vol. 24,
no. 4
p. 102379
Abstract
Summary: 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.
