Major ceRNA regulation and key metabolic signature analysis of intervertebral disc degeneration

Cao, Shuai; Li, Jie; Yang, Kai; Li, Haopeng

doi:10.1186/s12891-021-04109-8

“…Furthermore, to identify the critical ceRNAs that are regulated by the key IRG(s), other DERNAs were screened via SVM and expression-level analyses. 13 In addition, we used the LASSO method to identify gene signatures and obtain the respective coefficient values, and to fit the logistic LASSO regression, the glmnet package (version 2.0–16) was used.…”

Section: Methodsmentioning

confidence: 99%

Identification of a circRNA-mediated comprehensive ceRNA network in spinal cord injury pathogenesis

Zu

¹

,

Li

²

,

He

³

et al. 2022

Exp Biol Med (Maywood)

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RNAs are closely associated with human diseases; however, immune-related genes (IRGs) and their potential regulatory networks in relation to spinal cord injury (SCI) are still poorly understood. Here, we investigated the key IRGs as well as the competing endogenous RNA (ceRNA) mechanisms that are associated with SCI pathogenesis based on microarray datasets and the use of a rat SCI model. Specifically, four independent SCI microarray datasets from Gene Expression Omnibus (GEO) database were analyzed and, thereafter, differentially expressed IRGs were annotated via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Furthermore, based on the GEO datasets, differentially expressed RNAs (DERNAs), including DEcircRNAs, DEmiRNAs, and DEmRNAs were identified and interactions between them were also predicted using online databases, and to construct a circular RNA (circRNA) mediated ceRNA network, candidate RNAs were also identified. Furthermore, the support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO) methods were used for the identification of critical DERNAs, while differential gene expression was validated using the GSE20907 dataset. Our results were as follows. In the SCI microarray datasets, 32, 58, and 74 DEIRGs, DEcircRNAs, and DEmiRNAs were identified, respectively. In addition, GO and KEGG analyses showed that the DEIRGs were primarily enriched in neutrophil-mediated immunity and nuclear factor-kappa B (NF-κB) and hypoxia-inducible factor-1 (HIF-1) signaling pathways, and based on LASSO and SVM screening, PLXNB2 was identified as a DEIRG, while hsa_circ_0026646 was identified as the key circRNA, showing a higher SCI expression. Furthermore, our results proved that PLXNB2 and hsa_circ_0026646 were upregulated in SCI, whereas miR-331-3p was downregulated, and, interestingly, similar expression profiles were confirmed using the rat SCI model. Furthermore, fluorescent reporter assay indicated that both hsa_circ_0026646 and PLXNB2 have miR-331-3p target sites, and the ceRNA hypothesis suggested the dysregulation of hsa_circ_0026646, miR-331-3p, and PLXNB2 in SCI. Thus, our results suggested that in SCI pathogenesis, hsa_circ_0026646 correlates with PLXNB2 by targeting miR-331-3p.

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“…circRNA/lncRNA/miRNA/mRNA inhibits macrophage inflammation in type 1 diabetes mellitus (T1DM) (53). AC063977.6/miR-338-3p/PFKFB2 may regulate metabolic event during Intervertebral disc degeneration (IDD) pathogenesis (54). LncRNAs-based ceRNA reflects in circulating extracellular vesicles in human MetS (55).…”

Section: Discussionmentioning

confidence: 99%

Potential of ATP5MG to Treat Metabolic Syndrome-Associated Cardiovascular Diseases

Liu

¹

,

Zhou

²

,

Chen

³

et al. 2022

Front. Cardiovasc. Med.

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IntroductionMetabolic syndrome-associated cardiovascular disease (MetS-CVD) is a cluster of metabolism-immunity highly integrated diseases. Emerging evidence hints that mitochondrial energy metabolism may be involved in MetS-CVD development. The physiopathological role of ATP5MG, a subunit of the F0 ATPase complex, has not been fully elucidated.MethodsIn this study, we selected ATP5MG to identify the immunity-mediated pathway and mine drugs targeting this pathway for treating MetS-CVD. Using big data from public databases, we dissected co-expressed RNA (coRNA), competing endogenous RNA (ceRNA), and interacting RNA (interRNA) genes for ATP5MG.ResultsIt was identified that ATP5MG may form ceRNA with COX5A through hsa-miR-142-5p and interplay with NDUFB8, SOD1, and MDH2 through RNA–RNA interaction under the immune pathway. We dug out 251 chemicals that may target this network and identified some of them as clinical drugs. We proposed five medicines for treating MetS-CVD. Interestingly, six drugs are being tested to treat COVID-19, which unexpectedly offers a new potential host-targeting antiviral strategy.ConclusionCollectively, we revealed the potential significance of the ATP5MG-centered network for developing drugs to treat MetS-CVD, which offers insights into the epigenetic regulation for metabolism-immunity highly integrated diseases.

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“…For the sake of elucidating the underlying transcriptional regulation mechanisms among genes, an lncRNA-miRNA-mRNA triple ceRNA network was constructed in IS, as in previously reported similar methods [ 17 – 19 ]. According to the four online databases (miRcode, miRDB, miRTarBase, and TargetScan), we integrated lncRNA-miRNA pairs and miRNA-mRNA pairs into the ceRNA network, which was visualized by Cytoscape (v3.8.0) [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

Investigating the AC079305/DUSP1 Axis as Oxidative Stress-Related Signatures and Immune Infiltration Characteristics in Ischemic Stroke

Fan

¹

,

Cao

²

,

Chen

³

et al. 2022

Oxidative Medicine and Cellular Longevity

Self Cite

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Background. Oxidative stress (OS) and immune inflammation play complex intersections in the pathophysiology of ischemic stroke (IS). However, a competing endogenous RNA- (ceRNA-) based mechanism linked to the intersections in IS has not been explored. We aimed to identify potential OS-related signatures and analyze immune infiltration characteristics in IS. Methods. Three datasets (GSE22255, GSE110993, and GSE140275) from the GEO database were extracted. Differentially expressed long noncoding RNAs, microRNAs, and messenger RNAs (DElncRNAs, DEmiRNAs, and DEmRNAs) between IS patients and controls were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were explored. Moreover, a triple ceRNA network was constructed to reveal transcriptional regulation mechanisms. A comprehensive strategy among least absolute shrinkage and selection operator (LASSO) regression, DEmRNAs, uprelated DEmRNAs, and OS-related genes was adopted to select the best signature. Then, we evaluated and verified the discriminant ability of the signature via receiver operating characteristic (ROC) analysis. Immune infiltration characteristics were explored via the CIBERSORT algorithm. Moreover, the best signature was verified via qPCR and western blot methods in rat brain tissues and PC12 cells. Results. 11 DEmRNAs were identified totally. Enrichment analysis showed that the DEmRNAs were primarily concentrated in MAPK-associated biological processes and immune or inflammation-involved pathways. DUSP1 was identified as the best signature with an area under the ROC curve of 73.5% ( 95 % CI = 57.02 -89.98, sensitivity = 95 % , and specificity = 60 % ) in GSE22255 and 100.0% ( 95 % CI = 100.00 -100.00, sensitivity = 100 % , and specificity = 100 % ) in GSE140275. Importantly, we also identified the AC079305/DUSP1 axis in the ceRNA network. Immune infiltration showed that resting mast cells infiltrate less in IS patients compared with controls. And DUSP1 was negatively correlated with resting mast cells ( r = − 0.703 , P < 0.01 ), whereas it was positively correlated with neutrophils ( r = 0.339 , P < 0.05 ). Both in vivo and in vitro models confirmed the upregulated expression of DUSP1 and the downregulated expression of miR-429. Conclusion. This study identified the ceRNA-based AC079305/DUSP1 axis as a promising OS-related signature for IS. Immune infiltrating cells, especially mast cells, may exert a pivotal role in IS progression. Pharmacological agents targeting signatures, their receptors, or mast cells may shed a novel light on therapeutic targets for IS.

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Major ceRNA regulation and key metabolic signature analysis of intervertebral disc degeneration

Cited by 11 publications

References 43 publications

Identification of a circRNA-mediated comprehensive ceRNA network in spinal cord injury pathogenesis

Identification of a circRNA-mediated comprehensive ceRNA network in spinal cord injury pathogenesis

Potential of ATP5MG to Treat Metabolic Syndrome-Associated Cardiovascular Diseases

Investigating the AC079305/DUSP1 Axis as Oxidative Stress-Related Signatures and Immune Infiltration Characteristics in Ischemic Stroke

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