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Differentially expressed long non-coding RNAs and mRNAs in DRG of bone cancer pain and sham group rats based on microarray and bioinformatic analysis

ABSTRACT: Objective: The diagnostic roles of long non-coding RNAs (lncRNAs) and mRNAs in bone cancer pain are still not well defined. We aimed to identify differentially expressed DRG mRNAs in bone cancer pain and sham group rats systematically. Methods: Expression profile of mRNAs in DRG from bone cancer pain and sham group rats was analyzed by microarray assay. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway based approaches were used to investigate biological functions and signaling pathways affected by the differentially expressed mRNAs. GPR160 was selected for validation using Real-Time PCR. Results: Compared with sham group, a total of 807 differentially expressed mRNAs were revealed by heatmap and volcano-plot, including up-regulation in 720 and down-regulation in 87 (fold change ≥ 2 and P < 0.05), respectively. Pathways analysis based on upregulated mRNAs were mainly involved in antigen processing and presentation and phagosome pathway (P < 0.05). We first reported differentially expressed mRNAs in bone cancer pain and sham group rats systemically. Combined with the published dataset, we identified several differentially expressed mRNAs which might to be diagnostic or prognostic markers. The biological functions of those mRNAs should be further validated. Taken together, this study provided the basis for future treatment of bone cancer pain.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE270839 | GEO | 2024/12/18

REPOSITORIES: GEO

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Project description:Objective – Following destabilization of the medial meniscus (DMM), mice develop experimental osteoarthritis (OA) and associated pain behaviors that are dependent on the stage of disease. We aimed to describe changes in gene expression in knee-innervating dorsal root ganglia (DRG) after surgery, in order to identify molecular pathways associated with three pre-defined pain phenotypes: “post-surgical pain”, “early-stage OA pain”, and “persistent OA pain”. Design – We performed DMM or sham surgery in 10-week old male C57BL/6 mice and harvested L3-L5 DRG 4, 8, and 16 weeks after surgery or from age-matched naïve mice (n=3/group). RNA was extracted and an Affymetrix Mouse Transcriptome Array 1.0 was performed. Three pain phenotypes were defined: “post-surgical pain” (sham and DMM 4-week vs. 14-week old naïve), “early OA pain” (DMM 4-week vs. sham 4-week), and “persistent OA pain” (DMM 8- and 16-week vs. naïve and sham 8- and 16-week). ‘Top hit’ genes were defined as p<0.001. Pathway analysis (Ingenuity Pathway Analysis) was conducted using differentially expressed genes defined as p<0.05. In addition, we performed qPCR for Ngf and immunohistochemistry for F4/80+ macrophages in the DRG. Results – For each phenotype, top hit genes identified a small number of differentially expressed genes, some of which have been previously associated with pain (7/67 for “post-surgical pain”; 2/14 for “early OA pain”; 8/37 for “persistent OA pain”). Overlap between groups was limited, with 8 genes differentially regulated (p<0.05) in all three phenotypes. Pathway analysis showed that in the persistent OA pain phase many of the functions of differentially regulated genes are related to immune cell recruitment and activation. Genes previously linked to OA pain (CX3CL1, CCL2, TLR1, and NGF) were upregulated in this phenotype and contributed to activation of the neuroinflammation canonical pathway. In separate sets of mice, we confirmed that Ngf was elevated in the DRG 8 weeks after DMM (p=0.03), and numbers of F4/80+ macrophages were increased 16 weeks after DMM (p=0.002 vs. Sham). Conclusion- These transcriptomics findings support the idea that distinct molecular pathways discriminate early from persistent OA pain. Pathway analysis suggests neuroimmune interactions in the DRG contribute to initiation and maintenance of pain in OA. We grouped samples based on pain phenotype in the DMM mouse model of osteoarthritis. Group 1: post-surgical pain (DMM and sham +4 week samples); Group 2: post-surgical control (Naïve +4 week samples); Group 3: Early osteoarthritis pain (DMM +4 week samples); Group 4: Early controls (sham+4 and naive+4 week samples); Group 5: Persistent pain (DMM+8 and DMM+16 week samples); Group 6: Persistent controls (sham+8, naive+8, sham+16, and naive +16 samples). We compared Group 1 vs Group 2; Group 3 vs Group 4; and Group 5 vs Group 6 to draw the conclusions presented in our manuscript.

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Differentially expressed long non-coding RNAs and mRNAs in DRG of bone cancer pain and sham group rats based on microarray and bioinformatic analysis

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