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

Zijing Lin,Lijie Sun,Xiaorong Zhan,Yan Cao,Hui Qiu,Jie Gao,Xinyu Li

doi:10.1111/jcmm.13224

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.

Highlights

The increasing epidemic of type 2 diabetes mellitus (T2DM) and its comorbidities urge our understanding of the pathogenesis and regulatory mechanisms of T2DM [1]
Recent studies provide evidence that endogenous RNAs influence each other’s levels by competing for a limited pool of microRNAs [4]. competitive endogenous RNA (ceRNA) theory proposed that all types of RNA transcripts communicate through a new ‘language’ mediated by microRNA binding sites or microRNA response elements (MREs) [4]
We found that the mRNAs in DMCN were annotated into some diabetes-related pathways

Summary

Introduction

The increasing epidemic of T2DM and its comorbidities urge our understanding of the pathogenesis and regulatory mechanisms of T2DM [1]. The recent discovery of functional non-coding RNAs (ncRNAs) as specific gene expression regulators suggests that manipulating ncRNAs could be a novel therapeutic approach for combating metabolic disorders such as diabetes mellitus [2]. Numerous studies demonstrated that microRNAs have been implicated in diabetes mellitus [3]. Less is known about the regulatory role of lncRNAs in diabetes. Recent studies provide evidence that endogenous RNAs influence each other’s levels by competing for a limited pool of microRNAs [4]. Various ceRNA networks have been constructed to gain a global view of regulatory interaction networks of ceRNAs in certain diseases. Yang et al developed Starbase v 2.0 to systemically identify the RNA–RNA and protein–RNA interaction networks from 108

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Results

Conclusion