The Novel Regulatory Role of lncRNA-miRNA-mRNA Axis in Amyotrophic Lateral Sclerosis: An Integrated Bioinformatics Analysis.

Dingsheng Liu,Kaijie Chen,Rui Zhao,Changlian Lu,Xiaojia Zuo,Peng Zhang,Yuru Han,Guoqing Wan,Donglin Lai,Yanjun Zheng,Xuefeng Gu,Lei Chen

doi:10.1155/2021/5526179

Dingsheng Liu, Kaijie Chen + Show 10 more

Open Access

https://doi.org/10.1155/2021/5526179

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Abstract

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that primarily affects motor neurons, causing muscle atrophy, bulbar palsy, and pyramidal tract signs. However, the aetiology and pathogenesis of ALS have not been elucidated to date. In this study, a competitive endogenous RNA (ceRNA) network was constructed by analyzing the expression profiles of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) that were matched by 7 ALS samples and 4 control samples, and then a protein-protein interaction (PPI) network was constructed to identify the genes related to ALS. Gene Ontology (GO) was used to study the potential functions of differentially expressed mRNAs (DEmRNAs) in the ceRNA network. For the ALS and control groups, 247177 potential lncRNA-mRNA ceRNA relationship pairs were screened. Analysis of significant relationship pairs demonstrated that the PPI modules formed by the MALAT1-regulated SYNRG, ITSN2, PICALM, AP3B1, and AAK1 genes may play important roles in the pathogenesis of ALS, and these results may help to characterize the pathogenesis of ALS.

Highlights

Amyotrophic lateral sclerosis (ALS) is an incurable chronic neurological disease that can lead to the continuous death of upper and lower motor neurons, resulting in muscle atrophy and fatigue that affect the patient’s limb movement until the death of the patient [1,2,3,4]
Data on miRNA-long noncoding RNAs (lncRNAs) regulatory relationships were downloaded from the experimental module of the lncBase database, and miRNA-messenger RNAs (mRNAs) regulatory relationships were confirmed by experimental data downloaded from miRTarBase to ensure the accuracy of miRNA target gene prediction
We found that ALS samples and control samples were separated using t-Distributed Stochastic Neighbour Embedding (t-SNE) for dimensionality reduction visualization (Figure S1)

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is an incurable chronic neurological disease that can lead to the continuous death of upper and lower motor neurons, resulting in muscle atrophy and fatigue that affect the patient’s limb movement until the death of the patient [1,2,3,4]. This disease is most likely to occur in middle-aged people, with an incidence rate of 1.52.7 per 100,000 people observed; in addition, most patients die within 5 years after the onset of the disease, which has a severe impact on the physical and mental health of patients [1, 5, 6]. Regardless of whether there is a family history, the disease pathogenesis is related to mutations in genes including SOD1 [7, 12], OPTN [6, 13], UBQLN2 [11], C9orf72 [8], SQSTM1 [2], SETX [2], GARP [9], PFN1 [14], and SPG7 [15] and genes that encode RNA-binding proteins [16], such as TARDBP, hnRNPA2B1, hnRNPA1, and FUS

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