miR-300 通过靶向 HMGB1 减轻大鼠模型中的癌性骨痛。
miR-300 mitigates cancer-induced bone pain through targeting HMGB1 in rat models.
机构信息
Department of Anesthesiology, The First Affiliated Hospital of Soochow University, 899 Pinghai Street, Gusu District, 215006, Suzhou, Jiangsu, China.
Department of Anesthesiology, Gaoyou People's Hospital, Gaoyou Hospital Affiliated Soochow University, 225600, Yangzhou, Jiangsu, China.
出版信息
Genes Genomics. 2020 Mar;42(3):309-316. doi: 10.1007/s13258-019-00904-9. Epub 2019 Dec 23.
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.
背景
癌症骨痛（CIBP）是由恶性肿瘤骨转移引起的疼痛，也是癌症患者最大的疼痛来源。miR-300 是癌症中重要的 miRNA。已经表明，miR-300 调节各种肿瘤的肿瘤发生。
目的
本研究旨在探讨 miR-300 在 CIBP 中的作用及其在体内外的潜在分子机制。
方法
我们构建了大鼠 CIBP 模型，并通过研究 miR-300 影响 CIBP 的机制来进行探讨。我们首先检查了 CIBP 大鼠中 miR-300 的表达水平，然后测试了其过表达的效果。接下来，我们使用 TargetScan 分析和双荧光素酶报告基因实验鉴定了 miR-300 的靶标。最后，我们研究了 miR-300 与其靶标之间的遗传相互作用及其在 CIBP 中的作用。
结果
我们发现 miR-300 在 CIBP 大鼠中下调。miR-300 的过表达显著减轻了癌症引起的神经性疼痛（p<0.01）。此外，TargetScan 分析和双荧光素酶报告基因实验表明高迁移率族蛋白 1（HMGB1）是 miR-300 的靶标。值得注意的是，HMGB1 在 CIBP 大鼠中过度表达，而 miR-300 的上调显著抑制了 HMGB1 的表达（p<0.01）。此外，siRNA 敲低 HMGB1 显著缓解了大鼠的癌症引起的神经性疼痛（p<0.01）。另一方面，HMGB1 的过表达部分阻断了 miR-300 对癌症引起的神经痛的作用。
结论
miR-300 通过抑制 HMGB1 的表达缓解癌症引起的神经性疼痛。这些结果可能对临床实践中 CIBP 的治疗有益。
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