Chenglong Liu1, Xiaojuan Zha2, Haihua Liu3, Fang Wei4, Fei Zhang5. 1. Department of Anesthesiology, Gaoyou Hospital Affiliated Soochow University, Gaoyou People's Hospital, No. 116 Fuqian Street, Gaoyou City, Yangzhou City, 225600, Jiangsu Province, China. ChenglongLiuset@163.com. 2. Thyroid Center, Shanghai Research Center for Thyroid Diseases, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China. 3. Department of Neurology, Gaoyou Hospital Affiliated Soochow University, Gaoyou People's Hospital, Gaoyou City, 225600, Jiangsu Province, China. 4. Department of Radiology, Gaoyou Hospital Affiliated Soochow University, Gaoyou People's Hospital, Gaoyou City, 225600, Jiangsu Province, China. 5. Department of Anesthesiology, Gaoyou Hospital Affiliated Soochow University, Gaoyou People's Hospital, No. 116 Fuqian Street, Gaoyou City, Yangzhou City, 225600, Jiangsu Province, China.
Abstract
BACKGROUND: Cancer-induced bone pain (CIBP) is the pain caused by bone metastasis from malignant tumors, and the largest source of pain for cancer patients. miR-300 is an important miRNA in cancer. It has been shown that miR-300 regulates tumorigenesis of various tumors. PURPOSE: This study aims to investigate the role of miR-300 in CIBP and its underlying molecular mechanisms in vitro and in vivo. METHODS: We constructed CIBP model in rats and investigated the mechanism through which miR-300 affects CIBP. We first examined expression level of miR-300 in CIBP rats and then tested the effect of its overexpression. Next, we identified the target of miR-300 using TargetScan analysis and double luciferase assay. Finally, we studied genetic interactions between miR-300 and its target and their roles in CIBP. RESULTS: We found that miR-300 was downregulated in CIBP rats. Overexpression of miR-300 significantly attenuated cancer-induced neuropathic pain (p < 0.01). Furthermore, TargetScan analysis and double luciferase assay show High Mobility Group Box 1 (HMGB1) is a target of miR-300. Notably, HMGB1 is overexpressed in CIBP rats, while up-regulation of miR-300 significantly suppresses expression of HMGB1 (p < 0.01). Moreover, knockdown of HMGB1 by siRNA significantly relieves cancer-induced neuropathic pain in rats (p < 0.01). On the other hand, HMGB1 overexpression partially blocked the effect of miR-300 on cancer-induced nerve pain. CONCLUSION: miR-300 relieves cancer-induced neuropathic pain by inhibiting HMGB1 expression. These results may be beneficial for the treatment of CIBP in clinical practice.
BACKGROUND:Cancer-induced bone pain (CIBP) is the pain caused by bone metastasis from malignant tumors, and the largest source of pain for cancerpatients. miR-300 is an important miRNA in cancer. It has been shown that miR-300 regulates tumorigenesis of various tumors. PURPOSE: This study aims to investigate the role of miR-300 in CIBP and its underlying molecular mechanisms in vitro and in vivo. METHODS: We constructed CIBP model in rats and investigated the mechanism through which miR-300 affects CIBP. We first examined expression level of miR-300 in CIBP rats and then tested the effect of its overexpression. Next, we identified the target of miR-300 using TargetScan analysis and double luciferase assay. Finally, we studied genetic interactions between miR-300 and its target and their roles in CIBP. RESULTS: We found that miR-300 was downregulated in CIBP rats. Overexpression of miR-300 significantly attenuated cancer-induced neuropathic pain (p < 0.01). Furthermore, TargetScan analysis and double luciferase assay show High Mobility Group Box 1 (HMGB1) is a target of miR-300. Notably, HMGB1 is overexpressed in CIBP rats, while up-regulation of miR-300 significantly suppresses expression of HMGB1 (p < 0.01). Moreover, knockdown of HMGB1 by siRNA significantly relieves cancer-induced neuropathic pain in rats (p < 0.01). On the other hand, HMGB1 overexpression partially blocked the effect of miR-300 on cancer-induced nerve pain. CONCLUSION:miR-300 relieves cancer-induced neuropathic pain by inhibiting HMGB1 expression. These results may be beneficial for the treatment of CIBP in clinical practice.