KMID : 0381120200420030309
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Genes and Genomics 2020 Volume.42 No. 3 p.309 ~ p.316
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miR-300 mitigates cancer-induced bone pain through targeting HMGB1 in rat models
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Liu Chenglong
Yang Jianping Liu Haihua Xia Tian Zhang Fei
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Abstract
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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.
Objective: 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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KEYWORD
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Cancer-induced bone, Pain, miR-300, HMGB1, Neuropathic pain
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