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.
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Funding
This work was supported by the Yangzhou’s 13th Five-Year plan for “Ke Jiao Qiang Wei” (Grant No. ZDRC39) and Science and Technology Development Fundation of Clinical Medicine of Jiangsu University (Grant No. JLY20180167).
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CLL and XJZ conceived and designed the experiments, HHL and FW analyzed and interpreted the results of the experiments, FZ performed the experiments
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Liu, C., Zha, X., Liu, H. et al. Ampelopsin alleviates sevoflurane-induced cognitive dysfunction by mediating NF-κB pathway in aged rats. Genes Genom 42, 361–369 (2020). https://doi.org/10.1007/s13258-019-00897-5
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DOI: https://doi.org/10.1007/s13258-019-00897-5