Abstract

Bone cancer pain (BCP)–depression comorbidity has become a complex clinical problem during cancer treatment; however, its underlying molecular mechanisms have not been clarified. Several long noncoding RNAs (lncRNAs) have been demonstrated to be promising therapeutic targets in depression, but research on the role of lncRNAs in BCP–depression comorbidity has been limited. Therefore, high-throughput RNA sequencing was performed to detect differentially expressed profiles in the amygdala of a BCP–depression rat model in this study. We detected 330 differentially expressed mRNAs (DEmRNAs) and 78 differentially expressed lncRNAs (DElncRNAs) in the BCP–depression comorbidity model and then verified the expression of six DEmRNAs and six DElncRNAs with the greatest degrees of difference by RT-qPCR. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that differentially expressed genes were strongly enriched in inflammatory and immunologic systemic responses. Then the nuclear factor kappa B (NF-κB) signaling pathway and the Th17 differentiation pathway showed significant differences, as determined by Western blot analysis. Finally, we constructed a protein–protein interaction (PPI) network to explore the potential regulatory mechanism of DEmRNAs. In conclusion, our study reveals a new resource for the understanding of dysregulated lncRNAs and mRNAs in BCP–depression comorbidity and provides novel potential therapeutic targets for further approaches.

Highlights

  • Increased responsiveness to mechanical stimuli of the hind paw on postoperative days 7, 14, and 21 was observed in cancer-bearing rats compared with sham rats, in which responsiveness remained unchanged (Figure 1C, p < 0.001)

  • Rats that underwent the Sucrose preference test (SPT) and Forced swimming test (FST) before surgery were subjected to the SPT an FST again 25–26 days after surgery, and the results of the SPT showed a decreased pre erence for sucrose on postoperative day (POD) 25 (Figure 2A), while the total fluid con sumption was not altered in either group (Figure 2B)

  • These results indicate that the bone cancer pain (BCP)–depression comorbidity caused by tumor sion betweeninthe sham rats

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Summary

Introduction

Primary and metastatic cancers that invade the bone are frequently associated with severe and intractable bone cancer pain (BCP) [1]. BCP can lead to depression and seriously affect the living quality of patients; the severity of the depression, in turn, greatly affects the occurrence of BCP by aggravating the patient’s perception of pain and reducing the effect of analgesic treatment [2,3,4]. According to the latest data, 19.29 million new cases of cancer occur each year worldwide [5], and bone metastasis is the most common type of tumor metastasis in patients with advanced cancer [6], which increases the number of patients who suffer from BCP–depression comorbidity. Especially lncRNA regulation at the transcription level, is a critical part of gene expression modulation in all living organisms [8]

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