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Transcriptomic analysis of long noncoding RNAs and mRNAs expression profiles in the spinal cord of bone cancer pain
Xinran Hou1, Yingqi Weng1, Qulian Guo1
1Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China.
Abstract:
Bone cancer pain (BCP) is one of the most common types of chronic cancer pain and its pathogenesis has not been fully understood. Long non-coding RNAs (lncRNAs) are new promising targets in the field of pain research, however, their involvements in BCP have not been reported. In the present study, we established the BCP model by implantation of Walker 256 carcinoma cells into rats' tibial medullary cavity and performed transcriptome sequencing of the ipsilateral lumbar spinal cord to explore changes in expression profiles of lncRNA and mRNA. We identified 1220 differently expressed mRNAs (DEmRNAs) (1171 up-regulated and 49 down-regulated) and 323 differently expressed lncRNAs (DElncRNAs) (246 up-regulated and 77 down-regulated) in BCP model, among which 10 DEmRNAs (5 up-regulated and 5 down-regulated) and 10 DElncRNAs (5 up-regulated and 5 down-regulated) were validated the expression by RT-qPCR. Then, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on the expression of DEmRNAs and DElncRNAs, showing that they were mainly enriched in inflammatory and immunologic processes/pathways. Finally, we constructed a co-expression network and a ceRNA network of DEmRNAs and DElncRNAs to exhibit a potential regulatory mechanism of DElncRNAs, directly regulating protein coding gene expression in cis or in trans and indirectly regulating protein coding gene expression by sponging miRNA. In conclusion, our study provided a landscape of dysregulated lncRNA and mRNA in spinal cord of bone cancer pain and detected novel potential targets for treatment in the future.
Insights
This study reveals long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) are altered in bone cancer pain (BCP). These findings offer new therapeutic targets for managing chronic pain associated with cancer.
Area of Science:
- Molecular Biology
- Neuroscience
- Oncology
Background:
- Bone cancer pain (BCP) is a prevalent form of chronic cancer pain with incompletely understood mechanisms.
- Long non-coding RNAs (lncRNAs) are emerging as significant players in pain research, but their role in BCP remains unexplored.
Purpose of the Study:
- To investigate the differential expression profiles of lncRNAs and mRNAs in the spinal cord of a rat model of BCP.
- To identify potential regulatory networks and therapeutic targets for BCP.
Main Methods:
- Establishment of a rat model of BCP via Walker 256 carcinoma cell implantation.
- Transcriptome sequencing of the lumbar spinal cord to analyze lncRNA and mRNA expression.
- Validation of differentially expressed genes (DEGs) using RT-qPCR.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
- Construction of co-expression and competing endogenous RNA (ceRNA) networks.
Main Results:
- Identification of 1220 differentially expressed mRNAs (DEmRNAs) and 323 differentially expressed lncRNAs (DElncRNAs) in the BCP model.
- Validation of 10 DEmRNAs and 10 DElncRNAs.
- GO and KEGG analyses indicated enrichment in inflammatory and immunologic pathways.
- Construction of regulatory networks highlighting potential lncRNA-mediated gene regulation.
Conclusions:
- This study provides a comprehensive landscape of lncRNA and mRNA dysregulation in the spinal cord associated with BCP.
- Identified DElncRNAs and DEmRNAs represent potential therapeutic targets for future BCP treatments.
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