Integrative mRNA-microRNA analyses reveal novel interactions related to insulin sensitivity in human adipose tissue.

TitleIntegrative mRNA-microRNA analyses reveal novel interactions related to insulin sensitivity in human adipose tissue.
Publication TypeJournal Article
Year of Publication2016
AuthorsKirby TJ, R Walton G, Finlin B, Zhu B, Unal R, Rasouli N, Peterson CA, Kern PA
JournalPhysiol Genomics
Volume48
Issue2
Pagination145-53
Date Published2016 Feb
ISSN1531-2267
KeywordsADAM Proteins, Adipose Tissue, Cluster Analysis, G(M2) Activator Protein, Gene Expression Profiling, Gene Expression Regulation, Genome, Human, Humans, Insulin, Insulin Resistance, MicroRNAs, Myosin Heavy Chains, Myosin Type V, Nerve Tissue Proteins, Oligonucleotide Array Sequence Analysis, RNA, Messenger, Scavenger Receptors, Class E
Abstract

Adipose tissue has profound effects on whole-body insulin sensitivity. However, the underlying biological processes are quite complex and likely multifactorial. For instance, the adipose transcriptome is posttranscriptionally modulated by microRNAs, but the relationship between microRNAs and insulin sensitivity in humans remains to be determined. To this end, we utilized an integrative mRNA-microRNA microarray approach to identify putative molecular interactions that regulate the transcriptome in subcutaneous adipose tissue of insulin-sensitive (IS) and insulin-resistant (IR) individuals. Using the NanoString nCounter Human v1 microRNA Expression Assay, we show that 17 microRNAs are differentially expressed in IR vs. IS. Of these, 16 microRNAs (94%) are downregulated in IR vs. IS, including miR-26b, miR-30b, and miR-145. Using Agilent Human Whole Genome arrays, we identified genes that were predicted targets of miR-26b, miR-30b, and miR-145 and were upregulated in IR subjects. This analysis produced ADAM22, MYO5A, LOX, and GM2A as predicted gene targets of these microRNAs. We then validated that miR-145 and miR-30b regulate these mRNAs in differentiated human adipose stem cells. We suggest that use of bioinformatic integration of mRNA and microRNA arrays yields verifiable mRNA-microRNA pairs that are associated with insulin resistance and can be validated in vitro.

DOI10.1152/physiolgenomics.00071.2015
Alternate JournalPhysiol. Genomics
PubMed ID26672043
PubMed Central IDPMC4729698
Grant ListP20 GM103527 / GM / NIGMS NIH HHS / United States
DK-071349 / DK / NIDDK NIH HHS / United States
UL1 TR000117 / TR / NCATS NIH HHS / United States