Upregulation of Spinal miR-155-5p Contributes to Mechanical Hyperalgesia by Promoting Inflammatory Activation of Microglia in Bone Cancer Pain Rats
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...
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MDPI AG
2022-08-01
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| Online Access: | https://www.mdpi.com/2075-1729/12/9/1349 |
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| author | Yanping Jian Zongbin Song Zhuofeng Ding Jian Wang Ruike Wang Xinran Hou |
| author_facet | Yanping Jian Zongbin Song Zhuofeng Ding Jian Wang Ruike Wang Xinran Hou |
| author_sort | Yanping Jian |
| collection | DOAJ |
| description | 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 (<i>Sgk3</i>) 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 <i>Sgk3</i>-expression-attenuated microglial activation and alleviated hyperalgesia in the BCP rats. In conclusion, spinal miR-155-5p/<i>Sgk3</i>/microglial activation might play an important role in BCP pathogenesis. |
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| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T23:23:03Z |
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| spelling | doaj.art-08a6dc6ac5574c4d8153898c7c48543f2023-11-23T17:22:35ZengMDPI AGLife2075-17292022-08-01129134910.3390/life12091349Upregulation of Spinal miR-155-5p Contributes to Mechanical Hyperalgesia by Promoting Inflammatory Activation of Microglia in Bone Cancer Pain RatsYanping Jian0Zongbin Song1Zhuofeng Ding2Jian Wang3Ruike Wang4Xinran Hou5Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, ChinaBone 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 (<i>Sgk3</i>) 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 <i>Sgk3</i>-expression-attenuated microglial activation and alleviated hyperalgesia in the BCP rats. In conclusion, spinal miR-155-5p/<i>Sgk3</i>/microglial activation might play an important role in BCP pathogenesis.https://www.mdpi.com/2075-1729/12/9/1349bone cancer painmechanical hyperalgesiamiR-155-5p<i>Sgk3</i>microglia |
| spellingShingle | Yanping Jian Zongbin Song Zhuofeng Ding Jian Wang Ruike Wang Xinran Hou Upregulation of Spinal miR-155-5p Contributes to Mechanical Hyperalgesia by Promoting Inflammatory Activation of Microglia in Bone Cancer Pain Rats Life bone cancer pain mechanical hyperalgesia miR-155-5p <i>Sgk3</i> microglia |
| title | Upregulation of Spinal miR-155-5p Contributes to Mechanical Hyperalgesia by Promoting Inflammatory Activation of Microglia in Bone Cancer Pain Rats |
| title_full | Upregulation of Spinal miR-155-5p Contributes to Mechanical Hyperalgesia by Promoting Inflammatory Activation of Microglia in Bone Cancer Pain Rats |
| title_fullStr | Upregulation of Spinal miR-155-5p Contributes to Mechanical Hyperalgesia by Promoting Inflammatory Activation of Microglia in Bone Cancer Pain Rats |
| title_full_unstemmed | Upregulation of Spinal miR-155-5p Contributes to Mechanical Hyperalgesia by Promoting Inflammatory Activation of Microglia in Bone Cancer Pain Rats |
| title_short | Upregulation of Spinal miR-155-5p Contributes to Mechanical Hyperalgesia by Promoting Inflammatory Activation of Microglia in Bone Cancer Pain Rats |
| title_sort | upregulation of spinal mir 155 5p contributes to mechanical hyperalgesia by promoting inflammatory activation of microglia in bone cancer pain rats |
| topic | bone cancer pain mechanical hyperalgesia miR-155-5p <i>Sgk3</i> microglia |
| url | https://www.mdpi.com/2075-1729/12/9/1349 |
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