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Author Spotlight: A Computational Pipeline for Analyzing Chimeric Noncoding RNA-Target RNA Interactions in High-Throughput Sequencing Data
Published on: December 1, 2023
Analysis of Long Noncoding RNA and mRNA Expression Profiles in IL-9-Activated Astrocytes and EAE Mice
Xiaomei Liu1,2, Qing Zhang3, Weixiao Wang2
1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.
Background/Aims:
Multiple sclerosis (MS) is an autoimmune disease in the central nervous system associated with demyelination and axonal injury. Astrocyte activation is involved in the pathogenesis of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. This study was designed to find potential lncRNAs in EAE mice and activated astrocytes.
Methods:
we performed microarray analysis of lncRNAs from the brain tissues of EAE mice and primary mouse astrocytes treated with IL-9(50 ng/ml). 12 lncRNAs were validated through real-time PCR. Gene ontology and KEGG pathway analysis were applied to explore the potential functions of lncRNAs.
Results:
Differentially expressed 3300 lncRNAs and 3250 mRNAs were in the brain tissues of EAE mice, and 3748 lncRNAs and 3332 mRNAs were in activated astrocytes. Notably, there were 2 co-up-regulated lncRNAs and 3 co-down-regulated lncRNAs both in the brain tissues of EAE mice and in activated astrocytes, including Gm14005, Gm12478, mouselincRNA1117, AK080435, and mouselincRNA0681, which regulate the ER calcium flux kinetics, zinc finger protein and cell apoptosis. Similarly, there were 7 mRNAs co-up-regulated and 2 mRNAs co-down-regulated both in vivo and in vitro. Gene ontology and KEGG pathway analysis showed that the biological functions of differentially expressed mRNAs were associated with metabolism, development and inflammation. The results of realtime PCR validation were consistent with the data from the microarrays.
Conclusions:
Our data uncovered the expression profiles of lncRNAs and mRNAs in vivo and in vitro, which may help delineate the mechanisms of astrocyte activation during MS/EAE process.
Insights
This study identified key long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in a mouse model of Multiple Sclerosis (MS) and activated astrocytes. These findings offer insights into the molecular mechanisms underlying astrocyte activation in MS pathogenesis.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Multiple sclerosis (MS) is a central nervous system autoimmune disease characterized by demyelination and axonal injury.
- Astrocyte activation plays a significant role in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE).
Purpose of the Study:
- To identify novel long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) involved in the EAE mouse model.
- To investigate the role of astrocyte activation in the molecular changes observed in EAE.
Main Methods:
- Microarray analysis of lncRNAs and mRNAs in brain tissues of EAE mice and IL-9-stimulated primary mouse astrocytes.
- Validation of selected lncRNAs using real-time PCR.
- Gene ontology and KEGG pathway analysis to determine the functions of differentially expressed genes.
Main Results:
- Identification of thousands of differentially expressed lncRNAs and mRNAs in both EAE mice and activated astrocytes.
- Discovery of five co-regulated lncRNAs (Gm14005, Gm12478, mouselincRNA1117, AK080435, mouselincRNA0681) involved in ER calcium flux, zinc finger protein regulation, and apoptosis.
- Co-expression analysis revealed significant changes in mRNAs related to metabolism, development, and inflammation.
Conclusions:
- The study presents comprehensive expression profiles of lncRNAs and mRNAs in vivo and in vitro during the MS/EAE process.
- These findings contribute to understanding the molecular mechanisms of astrocyte activation in the context of MS.
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