Construction of competitive endogenous RNA network reveals regulatory role of long non-coding RNAs in type 2 diabetes mellitus

J Cell Mol Med. 2017 Dec;21(12):3204-3213. doi: 10.1111/jcmm.13224. Epub 2017 Jun 23.

Abstract

Increasing epidemic of type 2 diabetes mellitus (T2DM) and its comorbidities makes it urgent to understand the pathogenesis and regulatory mechanism. However, little is known about the regulatory role of lncRNAs in diabetes. Here, we constructed a T2DM-related competitive endogenous RNA (ceRNA) network (DMCN) to explore biological function of lncRNAs during the development of diabetes mellitus. This network contained 351 nodes including 98 mRNAs, 86 microRNAs and 167 lncRNAs. Functional analysis showed that the mRNAs in DMCN were annotated into some diabetes-related pathways. Furthermore, mTOR-centred subnetwork was extracted and ncRNA-involved mTOR pathway was established. Finally, we validated that NEAT1 was potentially communicated with mTOR signalling target protein mLST8 via the association with miR-181b. These findings provide significant insight into lncRNA regulatory network in T2DM.

Keywords: competitive endogenous RNA; long non-coding RNA; mTOR; miR-181b; type 2 diabetes mellitus.

MeSH terms

  • Base Pairing
  • Base Sequence
  • Cell Line
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Gene Expression Regulation
  • Gene Ontology
  • Gene Regulatory Networks*
  • Hepatocytes
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Sequence Annotation
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • mTOR Associated Protein, LST8 Homolog / genetics
  • mTOR Associated Protein, LST8 Homolog / metabolism

Substances

  • MIrn181 microRNA, human
  • MLST8 protein, human
  • MicroRNAs
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • RNA, Messenger
  • mTOR Associated Protein, LST8 Homolog
  • MTOR protein, human
  • TOR Serine-Threonine Kinases