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Published on: March 1, 2019
Exploration of the Differentially Expressed Long Noncoding RNAs and Genes of Morphine Tolerance via Bioinformatic
Yong Qiu1, Ling-Bing Meng2, Chen-Yi Di3
1Department of Anesthesiology and Beijing Hospital, National Center of Gerontology, Beijing, P.R. China.
Abstract:
Morphine tolerance is one of the most common complications in patients with chronic pain. Many patients with morphine tolerance have poor efficacy in the treatment of primary pain, and are accompanied by the side effects. Previous studies have found that many mechanisms are involved in morphine tolerance, but few researches could fully explain morphine tolerance, and no effective treatment for morphine tolerance has been found. One expression profiling data set was downloaded from the Gene Expression Omnibus (GEO) database. The probes would be transformed into the homologous gene symbol by means of the platform's annotation information. GEO2R was used to search for differentially expressed long noncoding RNAs (lncRNAs) and differentially expressed genes (DEGs) that were differentially expressed between spinal cord samples. Receiver operator characteristic curve analysis was performed to determine the ability of the hub lncRNAs to predict morphine tolerance. Through the principal component analysis, the intragroup data repeatability is fine in the GSE110115. A total of 10 genes were identified as hub genes from the protein-protein interaction network with degrees ≥10. Compared with the normal saline group, the expression levels of LncRNA XR_006440, XR_009493, AF196267, MRAK150340, and MRAK037188 were more downregulated, while the expression levels of MRAK046606, XR_005988, DQ266361, uc.167-, and uc.468+ were more upregulated in the morphine tolerance group. LncRNAs and DEGs were differentially expressed between the morphine tolerance group and nonmorphine tolerance group, which may be involved in the development of morphine tolerance, especially LncRNA DQ266361, uc.167-, and Mmp9, CCL7 genes.
Insights
Morphine tolerance, a common complication in chronic pain, involves altered long noncoding RNA (lncRNA) and gene expression in the spinal cord. Identifying these molecular markers may lead to new therapeutic strategies for pain management.
Area of Science:
- Pharmacology and Molecular Biology
- Genomics and Bioinformatics
- Pain Research
Background:
- Morphine tolerance significantly reduces treatment efficacy for chronic pain and presents adverse side effects.
- Existing research on morphine tolerance mechanisms is incomplete, and effective treatments remain elusive.
- Understanding the molecular underpinnings of morphine tolerance is crucial for developing targeted therapies.
Purpose of the Study:
- To identify differentially expressed long noncoding RNAs (lncRNAs) and genes in the spinal cord associated with morphine tolerance.
- To explore the potential of specific lncRNAs as biomarkers for predicting morphine tolerance.
- To elucidate novel molecular pathways involved in the development of morphine tolerance.
Main Methods:
- Utilized a gene expression dataset from the Gene Expression Omnibus (GEO) database (GSE110115).
- Employed GEO2R to identify differentially expressed lncRNAs and genes (DEGs) between morphine-tolerant and non-tolerant spinal cord samples.
- Constructed a protein-protein interaction network to identify hub genes and performed Receiver Operating Characteristic (ROC) curve analysis for lncRNA predictive ability.
Main Results:
- Identified 10 hub genes from the protein-protein interaction network.
- Found significant differential expression of several lncRNAs, with some downregulated (e.g., XR_006440) and others upregulated (e.g., DQ266361, uc.167-) in the morphine tolerance group.
- Highlighted lncRNA DQ266361, uc.167-, and genes Mmp9 and CCL7 as potentially critical players in morphine tolerance development.
Conclusions:
- Differential expression of lncRNAs and DEGs in the spinal cord is associated with morphine tolerance.
- Specific lncRNAs, such as DQ266361 and uc.167-, show potential as predictive biomarkers for morphine tolerance.
- The identified genes and lncRNAs offer novel targets for future research into effective morphine tolerance treatments.
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