Identification of lncRNA and mRNA expression profiles in dorsal root ganglion in rats with cancer-induced bone pain.

BACKGROUND

Cancer-induced bone pain (CIBP) is one of the most severe types of chronic pain which the involved mechanisms are largely unknown. LncRNA has been found to play critical roles in chronic pain. However, its function in peripheral nervous system in CIBP remains unknown. Identifying the different lncRNA expression pattern is essential for understanding the genetic mechanisms underlying the pathogenesis of CIBP.

METHODS

The model was induced by injection of Walker 256 cells into the rat tibia canal. Behavior tests and X-ray microtomography (MicroCT) analysis were performed to verify the model's establishment. L2-L5 DRGs were harvested at 14-day post operation and the differential lncRNA and mRNA expression patterns were investigated by microarray analyses. RT-qPCR analysis and RNA interference were performed for expression and function verifications. Bioinformatics analysis was conducted for further function study.

RESULTS

CIBP rats showed hyperalgesia and the MicroCT analysis showed tibia destruction. A total of 73 lncRNAs and 187 mRNAs were dysregulated. The expressions of several lncRNAs and mRNAs were validated by RT-qPCR experiment. Biological analyses showed that the changed mRNAs were mainly related to cellular and single-organism process, cell and cell part, binding function and immune system pathway. The top 30 lncRNA-predicted mRNAs are mainly related to peroxisome, DNA-dependent DNA replication, double-stranded RNA binding, tuberculosis and purine metabolism. 56 lncRNAs (30 downregulated and 26 upregulated) and 179 DEGs (35 downregulated and 144 upregulated) have a significant correlation and constructed a co-expression network. Downregulation of lncRNA NONRATT021203.2 by siRNA intrathecal injection increased PWL and WBD in CIBP rats, alleviating cancer induced bone hyperalgesia.

CONCLUSION

LncRNA played important roles in regulation of CIBP or mRNA expression in peripheral neuropathy in CIBP. These alterd mRNAs and lncRNAs might be potential therapeutic targets for the treatment of CIBP.