An lncRNA-miRNA-mRNA-ceRNA network regulates intervertebral disc degeneration: A bioinformatics study based on the dataset analysis

Fan, Xutao; Chen, Guowu; Ma, Fengyu; Qi, Bao X.; Liang, Yanhu; Gopng, Pihao; Meng, Chunyang

doi:10.4149/gpb_2021013

Cited by 9 publications

(5 citation statements)

References 47 publications

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“…LncRNA can affect the gene expression by competitively binding miRNAs, namely, ceRNA mechanism, which has been proved to play important and complicated roles in the initiation or progression of human diseases, including IDD [15,50,51] circular RNAs in the progression of IDD were described based on the latest literatures, which suggested that noncoding RNAs could serve as potential targets for the IDD treatment [53]. Moreover, a bioinformatic analysis conducted by Wang et al showed that miRNAs could function as novel targets for preventing and treating IDD by regulating their target genes [54].…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress in Intervertebral Disc Degeneration: New Insights from Bioinformatic Strategies

Zhao

Xiang

Lin

et al. 2022

Oxidative Medicine and Cellular Longevity

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Oxidative stress has been proved to play important roles in the development of intervertebral disc degeneration (IDD); however, the underlying mechanism remains obscure to date. The aim of this study was to elucidate the vital roles of oxidative stress-related genes in the development of IDD using strict bioinformatic algorithms. The microarray data relevant to the IDD was downloaded from Gene Expression Omnibus database for further analysis. A series of bioinformatic strategies were used to determine the oxidative stress-related and IDD-related genes (OSIDDRGs), perform the function enrichment analysis and protein-protein interaction analysis, construct the lncRNA-miRNA-mRNA regulatory network, and investigate the potential relationship of oxidative stress to immunity abnormality and autophagy in IDD. We observed a significantly different status of oxidative stress between normal intervertebral disc tissues and IDD tissues. A total of 72 OSIDDRGs were screened out for the further function enrichment analysis, and 10 hub OSIDDRGs were selected to construct the lncRNA-miRNA-mRNA regulatory network. There was a very close association of oxidative stress with immunity abnormality and autophagy in IDD. Taken together, our findings can provide new insights into the mechanism research of oxidative stress in the development of IDD and offer new potential targets for the treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Oxidative Stress in Intervertebral Disc Degeneration: New Insights from Bioinformatic Strategies

Zhao

Xiang

Lin

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…miRTarBase is the key database, and all data have been verified experimentally. Genes predicted by miRTarBase and one of the other two databases were considered the target genes of DEMs [ 19 ]. Following the alignment of DEMs and DEGs, the Cytoscape software (v 3.9.1) was used to visualize the miRNA-mRNA regulatory network [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

Osteoarthritis related epigenetic variations in miRNA expression and DNA methylation

Jin

Chen

et al. 2023

BMC Med Genomics

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Osteoarthritis (OA) is chronic arthritis characterized by articular cartilage degradation. However, a comprehensive regulatory network for OA-related microRNAs and DNA methylation modifications has yet to be established. Thus, we aimed to identify epigenetic changes in microRNAs and DNA methylation and establish the regulatory network between miRNAs and DNA methylation. The mRNA, miRNA, and DNA methylation expression profiles of healthy or osteoarthritis articular cartilage samples were downloaded from Gene Expression Omnibus (GEO) database, including GSE169077, GSE175961, and GSE162484. The differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs), and differentially methylated genes (DMGs) were analyzed by the online tool GEO2R. DAVID and STRING databases were applied for functional enrichment analysis and protein-protein interaction (PPI) network. Potential therapeutic compounds for the treatment of OA were identified by Connectivity map (CMap) analysis. A total of 1424 up-regulated DEGs, 1558 down-regulated DEGs, 5 DEMs with high expression, 6 DEMs with low expression, 1436 hypermethylated genes, and 455 hypomethylated genes were selected. A total of 136 up-regulated and 65 downregulated genes were identified by overlapping DEGs and DEMs predicted target genes which were enriched in apoptosis and circadian rhythm. A total of 39 hypomethylated and 117 hypermethylated genes were obtained by overlapping DEGs and DMGs, which were associated with ECM receptor interactions and cellular metabolic processes, cell connectivity, and transcription. Moreover, The PPI network showed COL5A1, COL6A1, LAMA4, T3GAL6A, and TP53 were the most connective proteins. After overlapping of DEGs, DMGs and DEMs predicted targeted genes, 4 up-regulated genes and 11 down-regulated genes were enriched in the Axon guidance pathway. The top ten genes ranked by PPI network connectivity degree in the up-regulated and downregulated overlapping genes of DEGs and DMGs were further analyzed by the CMap database, and nine chemicals were predicted as potential drugs for the treatment of OA. In conclusion, TP53, COL5A1, COL6A1, LAMA4, and ST3GAL6 may play important roles in OA genesis and development.

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“…Micro-RNA list was imported to the miRWalk 3.0 online database to predict target genes, which comprises three sub-databases, namely, miRDB, Targetscan, and miRTarBase. Among them, miRTarBase was the unique database, of which all the data have been experimentally validated ( Fan et al, 2021 ). As a result, the genes predicted by miRTarBase w/o other two databases were considered to be the target genes of DEM.…”

Section: Methodsmentioning

confidence: 99%

Epigenetic Biomarkers Screening of Non-Coding RNA and DNA Methylation Based on Peripheral Blood Monocytes in Smokers

Huang

Zhang

et al. 2022

Front. Genet.

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This study aims to use bioinformatics methods to determine the epigenetic changes in microRNA expression and DNA methylation caused by cigarette smoking. The data of mRNA, miRNA expression, and methylation microarray were obtained from the GEO database to filter differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs), and methylated CpG probes (DMPs) through the limma package. The R clusterProfile package was used for functional annotation and enrichment analysis. The protein-protein interaction (PPI) network was constructed by the String database and visualized in Cytoscape software. Starbase database was employed to predict lncRNA and CirRNA based on the sequence of miRNA, and to establish a regulatory network of ceRNA. By overlapping DEG and DEM, 107 down-miRNA-targeted up-regulated genes and 65 up-miRNA-target down-regulated genes were obtained, which were mainly enriched in autophagy signaling pathways and protein ubiquitination pathways, respectively. In addition, 324 genes with low methylation and high expression and 204 genes with high methylation and low expression were respectively related to the degeneration of the nervous system and the function of the cardiovascular system. Interestingly, 43 genes were up-regulated under the dual regulation of reduced miRNA and hypomethylation, while 14 genes were down-regulated under the dual regulation of increased miRNA and hypermethylation. Ten chemicals have been identified as putative therapeutic agents for pathological conditions caused by smoking. In addition, among these genes, HSPA4, GRB2, PRKCA, and BCL2L1 could play a fundamental role in related diseases caused by smoking and may be used as the biomarkers for precise diagnosis and targets for future therapies of smoking-related diseases.

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An lncRNA-miRNA-mRNA-ceRNA network regulates intervertebral disc degeneration: A bioinformatics study based on the dataset analysis

Cited by 9 publications

References 47 publications

Oxidative Stress in Intervertebral Disc Degeneration: New Insights from Bioinformatic Strategies

Oxidative Stress in Intervertebral Disc Degeneration: New Insights from Bioinformatic Strategies

Osteoarthritis related epigenetic variations in miRNA expression and DNA methylation

Epigenetic Biomarkers Screening of Non-Coding RNA and DNA Methylation Based on Peripheral Blood Monocytes in Smokers

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