Transcriptomic analysis of long noncoding RNAs and mRNAs expression profiles in the spinal cord of bone cancer pain rats

Xinran Hou,Jiajia Dai,Qulian Guo,Zongbin Song,Anqi Wei,Yingqi Weng,Jian Wang,Zhuofeng Ding

doi:10.1186/s13041-020-00589-2

Xinran Hou, Jiajia Dai + Show 6 more

Open Access

https://doi.org/10.1186/s13041-020-00589-2

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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.

Highlights

Cancer pain, caused by primary cancer itself or metastases [1], often deteriorates the quality of life of cancer patients, with a prevalence rate of 50.7% in all cancer stages and 66.4% in advanced stage [2]
The development of Bone cancer pain (BCP) is accompanied by changes in numerous genes expression in the peripheral and central nervous system, which may account for this dysfunctional nociceptive perception [6,7,8]
The differences in paw withdrawal mechanical threshold (PWMT) between the two groups were significant on day 6, 8, 10, 12 and 14 after modeling (P < 0.01 and P < 0.001 respectively), indicating the development of mechanical hypersensitivity in BCP rats (Fig. 1a, Additional file 1 Table S1)

Summary

Introduction

Cancer pain, caused by primary cancer itself or metastases [1], often deteriorates the quality of life of cancer patients, with a prevalence rate of 50.7% in all cancer stages and 66.4% in advanced stage [2]. The development of BCP is accompanied by changes in numerous genes expression in the peripheral and central nervous system, which may account for this dysfunctional nociceptive perception [6,7,8]. Hou et al Molecular Brain (2020) 13:47 shown that dysregulated HDACs and its potential downstream targets in the lumbar spinal cord contribute to the development of BCP [9, 10]. Endogenous noncoding RNAs are another key regulators to modify the expression of mRNAs or protein targets, thereby contributing to the development of pathologic pain [11]

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