Construction of Glycometabolism- and Hormone-Related lncRNA-Mediated Feedforward Loop Networks Reveals Global Patterns of lncRNAs and Drug Repurposing in Gestational Diabetes

Front Endocrinol (Lausanne). 2020 Mar 6:11:93. doi: 10.3389/fendo.2020.00093. eCollection 2020.


Gestational diabetes mellitus (GDM) is a condition associated with the onset of abnormal glucose tolerance during pregnancy. Long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and genes can form lncRNA-mediated feedforward loops (lnc-FFLs), which are functional network motifs that regulate a wide range of biological processes and diseases. However, lnc-FFL network motifs have not been systematically investigated in GDM, and their role in the disease remains largely unknown. In the present study, a global lnc-FFL network was constructed and analyzed. Glycometabolism- and hormone-related lnc-FFL networks were extracted from the global network. An integrated algorithm was designed to identify dysregulated glycometabolism- and hormone-related lnc-FFLs in GDM. The patterns of dysregulated lnc-FFLs in GDM were complex. Moreover, there were strong associations between dysregulated glycometabolism- and hormone-related lnc-FFLs in GDM. Core modules were extracted from the dysregulated lnc-FFL networks in GDM and showed specific and essential functions. In addition, dysregulated lnc-FFLs could combine with ceRNAs and form more complex modules, which could play novel roles in GDM. Notably, we discovered that the dysregulated lnc-FFLs were enriched in the thyroid hormone signaling pathway. Some drug-repurposing candidates, such as hormonal drugs, could be identified based on lnc-FFLs in GDM. In summary, the present study highlighted the effect of dysregulated glycometabolism- and hormone-related lnc-FFLs in GDM and revealed their potential for the discovery of novel biomarkers and therapeutic targets for GDM.

Keywords: drug repurposing; gestational diabetes; glycometabolism; hormone; lncRNA-mediated feedforward loop; thyroid hormone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / analysis
  • Diabetes, Gestational / drug therapy
  • Diabetes, Gestational / genetics
  • Diabetes, Gestational / metabolism
  • Diabetes, Gestational / pathology*
  • Drug Repositioning*
  • Feedback, Physiological*
  • Female
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Glucose / metabolism*
  • Hormones / metabolism*
  • Humans
  • MicroRNAs / genetics*
  • Pregnancy
  • RNA, Long Noncoding / genetics*
  • Signal Transduction


  • Biomarkers
  • Hormones
  • MicroRNAs
  • RNA, Long Noncoding
  • Glucose