An Oxidative Stress-Related Gene Pair (CCNB1/PKD1), Competitive Endogenous RNAs, and Immune-Infiltration Patterns Potentially Regulate Intervertebral Disc Degeneration Development

Oxidative stress (OS) irreversibly affects the pathogenesis of intervertebral disc degeneration (IDD). Certain non-coding RNAs act as competitive endogenous RNAs (ceRNAs) that regulate IDD progression. Analyzing the signatures of oxidative stress-related gene (OSRG) pairs and regulatory ceRNA mechan...

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Autores principales:	Shuai Cao, Hao Liu, Jiaxin Fan, Kai Yang, Baohui Yang, Jie Wang, Jie Li, Liesu Meng, Haopeng Li
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	intervertebral disc degeneration oxidative stress gene pair immune infiltration competitive endogenous RNA differential expression Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/f6e0ad8ce8ad48c396aa7306aadd0d91
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spelling	oai:doaj.org-article:f6e0ad8ce8ad48c396aa7306aadd0d912021-11-09T06:34:15ZAn Oxidative Stress-Related Gene Pair (CCNB1/PKD1), Competitive Endogenous RNAs, and Immune-Infiltration Patterns Potentially Regulate Intervertebral Disc Degeneration Development1664-322410.3389/fimmu.2021.765382https://doaj.org/article/f6e0ad8ce8ad48c396aa7306aadd0d912021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.765382/fullhttps://doaj.org/toc/1664-3224Oxidative stress (OS) irreversibly affects the pathogenesis of intervertebral disc degeneration (IDD). Certain non-coding RNAs act as competitive endogenous RNAs (ceRNAs) that regulate IDD progression. Analyzing the signatures of oxidative stress-related gene (OSRG) pairs and regulatory ceRNA mechanisms and immune-infiltration patterns associated with IDD may enable researchers to distinguish IDD and reveal the underlying mechanisms. In this study, OSRGs were downloaded and identified using the Gene Expression Omnibus database. Functional-enrichment analysis revealed the involvement of oxidative stress-related pathways and processes, and a ceRNA network was generated. Differentially expressed oxidative stress-related genes (De-OSRGs) were used to construct De-OSRG pairs, which were screened, and candidate De-OSRG pairs were identified. Immune cell-related gene pairs were selected via immune-infiltration analysis. A potential long non-coding RNA–microRNA–mRNA axis was determined, and clinical values were assessed. Eighteen De-OSRGs were identified that were primarily related to intricate signal-transduction pathways, apoptosis-related biological processes, and multiple kinase-related molecular functions. A ceRNA network consisting of 653 long non-coding RNA–microRNA links and 42 mRNA–miRNA links was constructed. Three candidate De-OSRG pairs were screened out from 13 De-OSRG pairs. The abundances of resting memory CD4+ T cells, resting dendritic cells, and CD8+ T cells differed between the control and IDD groups. CD8+ T cell infiltration correlated negatively with cyclin B1 (CCNB1) expression and positively with protein kinase D1 (PKD1) expression. CCNB1–PKD1 was the only pair that was differentially expressed in IDD, was correlated with CD8+ T cells, and displayed better predictive accuracy compared to individual genes. The PKD1–miR-20b-5p–AP000797 and CCNB1–miR-212-3p–AC079834 axes may regulate IDD. Our findings indicate that the OSRG pair CCNB1–PKD1, which regulates oxidative stress during IDD development, is a robust signature for identifying IDD. This OSRG pair and increased infiltration of CD8+ T cells, which play important roles in IDD, were functionally associated. Thus, the OSRG pair CCNB1–PKD1 is promising target for treating IDD.Shuai CaoHao LiuJiaxin FanKai YangBaohui YangJie WangJie LiLiesu MengLiesu MengHaopeng LiFrontiers Media S.A.articleintervertebral disc degenerationoxidative stressgene pairimmune infiltrationcompetitive endogenous RNAdifferential expressionImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	intervertebral disc degeneration oxidative stress gene pair immune infiltration competitive endogenous RNA differential expression Immunologic diseases. Allergy RC581-607
spellingShingle	intervertebral disc degeneration oxidative stress gene pair immune infiltration competitive endogenous RNA differential expression Immunologic diseases. Allergy RC581-607 Shuai Cao Hao Liu Jiaxin Fan Kai Yang Baohui Yang Jie Wang Jie Li Liesu Meng Liesu Meng Haopeng Li An Oxidative Stress-Related Gene Pair (CCNB1/PKD1), Competitive Endogenous RNAs, and Immune-Infiltration Patterns Potentially Regulate Intervertebral Disc Degeneration Development
description	Oxidative stress (OS) irreversibly affects the pathogenesis of intervertebral disc degeneration (IDD). Certain non-coding RNAs act as competitive endogenous RNAs (ceRNAs) that regulate IDD progression. Analyzing the signatures of oxidative stress-related gene (OSRG) pairs and regulatory ceRNA mechanisms and immune-infiltration patterns associated with IDD may enable researchers to distinguish IDD and reveal the underlying mechanisms. In this study, OSRGs were downloaded and identified using the Gene Expression Omnibus database. Functional-enrichment analysis revealed the involvement of oxidative stress-related pathways and processes, and a ceRNA network was generated. Differentially expressed oxidative stress-related genes (De-OSRGs) were used to construct De-OSRG pairs, which were screened, and candidate De-OSRG pairs were identified. Immune cell-related gene pairs were selected via immune-infiltration analysis. A potential long non-coding RNA–microRNA–mRNA axis was determined, and clinical values were assessed. Eighteen De-OSRGs were identified that were primarily related to intricate signal-transduction pathways, apoptosis-related biological processes, and multiple kinase-related molecular functions. A ceRNA network consisting of 653 long non-coding RNA–microRNA links and 42 mRNA–miRNA links was constructed. Three candidate De-OSRG pairs were screened out from 13 De-OSRG pairs. The abundances of resting memory CD4+ T cells, resting dendritic cells, and CD8+ T cells differed between the control and IDD groups. CD8+ T cell infiltration correlated negatively with cyclin B1 (CCNB1) expression and positively with protein kinase D1 (PKD1) expression. CCNB1–PKD1 was the only pair that was differentially expressed in IDD, was correlated with CD8+ T cells, and displayed better predictive accuracy compared to individual genes. The PKD1–miR-20b-5p–AP000797 and CCNB1–miR-212-3p–AC079834 axes may regulate IDD. Our findings indicate that the OSRG pair CCNB1–PKD1, which regulates oxidative stress during IDD development, is a robust signature for identifying IDD. This OSRG pair and increased infiltration of CD8+ T cells, which play important roles in IDD, were functionally associated. Thus, the OSRG pair CCNB1–PKD1 is promising target for treating IDD.
format	article
author	Shuai Cao Hao Liu Jiaxin Fan Kai Yang Baohui Yang Jie Wang Jie Li Liesu Meng Liesu Meng Haopeng Li
author_facet	Shuai Cao Hao Liu Jiaxin Fan Kai Yang Baohui Yang Jie Wang Jie Li Liesu Meng Liesu Meng Haopeng Li
author_sort	Shuai Cao
title	An Oxidative Stress-Related Gene Pair (CCNB1/PKD1), Competitive Endogenous RNAs, and Immune-Infiltration Patterns Potentially Regulate Intervertebral Disc Degeneration Development
title_short	An Oxidative Stress-Related Gene Pair (CCNB1/PKD1), Competitive Endogenous RNAs, and Immune-Infiltration Patterns Potentially Regulate Intervertebral Disc Degeneration Development
title_full	An Oxidative Stress-Related Gene Pair (CCNB1/PKD1), Competitive Endogenous RNAs, and Immune-Infiltration Patterns Potentially Regulate Intervertebral Disc Degeneration Development
title_fullStr	An Oxidative Stress-Related Gene Pair (CCNB1/PKD1), Competitive Endogenous RNAs, and Immune-Infiltration Patterns Potentially Regulate Intervertebral Disc Degeneration Development
title_full_unstemmed	An Oxidative Stress-Related Gene Pair (CCNB1/PKD1), Competitive Endogenous RNAs, and Immune-Infiltration Patterns Potentially Regulate Intervertebral Disc Degeneration Development
title_sort	oxidative stress-related gene pair (ccnb1/pkd1), competitive endogenous rnas, and immune-infiltration patterns potentially regulate intervertebral disc degeneration development
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/f6e0ad8ce8ad48c396aa7306aadd0d91
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An Oxidative Stress-Related Gene Pair (CCNB1/PKD1), Competitive Endogenous RNAs, and Immune-Infiltration Patterns Potentially Regulate Intervertebral Disc Degeneration Development

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