Upregulation of Spinal miR-155-5p Contributes to Mechanical Hyperalgesia by Promoting Inflammatory Activation of Microglia in Bone Cancer Pain Rats

Abstract

Bone cancer pain (BCP) seriously deteriorates the life quality of patients, but its underlying mechanism is still unclear. Spinal microRNAs might contribute to the development of BCP and the role of microglial activation is controversial. In this study, we established a BCP model by injecting Walker 256 breast carcinoma cells into the tibial intramedullary cavity of rats and significant hyperalgesia was observed in the BCP rats. The lumbar spinal cords were harvested to perform RNA sequencing (RNA-seq), and 31 differentially expressed miRNAs (26 upregulated and 5 downregulated) were identified in the BCP rats. Among them, miR-155-5p was significantly upregulated in the BCP rats. Spinal microglial activation was observed during BCP development. miR-155-5p could be expressed in spinal microglia and was significantly upregulated in microglia treated with lipopolysaccharide (LPS) in vitro. Serum/glucocorticoid regulated kinase family member 3 (Sgk3) was predicted to be the possible downstream target of miR-155-5p and this was confirmed using a dual-luciferase reporter assay in vitro. The inhibition of miR-155-5p restored Sgk3-expression-attenuated microglial activation and alleviated hyperalgesia in the BCP rats. In conclusion, spinal miR-155-5p/Sgk3/microglial activation might play an important role in BCP pathogenesis.

Keywords

• bone cancer pain
• mechanical hyperalgesia
• miR-155-5p
• <i>Sgk3</i>
• microglia