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

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

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1016/j.isci.2021.102379
Journal or Publication Title: iScience
Volume: 24
Number: 4
Page Range: p. 102379
Date: 2021
Divisions: Vascular Biology
Depositing User: General Admin
Identification Number: 10.1016/j.isci.2021.102379
ISSN: 25890042
Date Deposited: 10 Jun 2021 01:02
Abstract:

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.

Keywords: Computational Bioinformatics; Pathophysiology; Transcriptomics.

© 2021 The Authors.

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Wong, Wilson K.M.
UNSPECIFIED
Joglekar, Mugdha V.
UNSPECIFIED
Saini, Vijit
UNSPECIFIED
Jiang, Guozhi
UNSPECIFIED
Dong, Charlotte X.
UNSPECIFIED
Chaitarvornkit, Alissa
UNSPECIFIED
Maciag, Grzegorz J.
UNSPECIFIED
Gerace, Dario
UNSPECIFIED
Farr, Ryan J.
UNSPECIFIED
Satoor, Sarang N.
UNSPECIFIED
Sahu, Subhshri
UNSPECIFIED
Sharangdhar, Tejaswini
UNSPECIFIED
Ahmed, Asma S.
UNSPECIFIED
Chew, Yi Vee
UNSPECIFIED
Liuwantara, David
UNSPECIFIED
Heng, Benjamin
UNSPECIFIED
Lim, Chai K.
UNSPECIFIED
Hunter, Julie
UNSPECIFIED
Januszewski, Andrzej S.
UNSPECIFIED
Sørensen, Anja E.
UNSPECIFIED
Akil, Ammira S.A.
UNSPECIFIED
Gamble, Jennifer R.
UNSPECIFIED
Loudovaris, Thomas
UNSPECIFIED
Kay, Thomas W.
UNSPECIFIED
Thomas, Helen E.
UNSPECIFIED
O'Connell, Philip J.
UNSPECIFIED
Guillemin, Gilles J.
UNSPECIFIED
Martin, David
UNSPECIFIED
Simpson, Ann M.
UNSPECIFIED
Hawthorne, Wayne J.
UNSPECIFIED
Dalgaard, Louise T.
UNSPECIFIED
Ma, Ronald C.W.
UNSPECIFIED
Hardikar, Anandwardhan A.
UNSPECIFIED
Last Modified: 10 Jun 2021 01:02
URI: https://eprints.centenary.org.au/id/eprint/986

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