脊髓中lncRNA NONRATT009773.2通过miR-708-5p/CXCL13轴调控骨癌痛的机制研究

骨癌痛是癌症患者骨转移后最常见的临床症状之一。虽然长链非编码RNA（lncRNA）在慢性疼痛的发生发展中起重要作用，但脊髓水平lncRNA在骨癌痛中的作用机制尚无报道。我们前期研究发现：骨癌痛大鼠脊髓中lncRNA NONRATT009773.2表达显著增加，抑制其表达可以缓解骨癌痛、增加miR-708-5p表达、进而使CXCL13表达降低。据此我们提出课题设想：lncRNA NONRATT009773.2通过miR-708-5p/CXCL13轴调控骨癌痛。为验证该假说，本项目拟建立骨癌痛模型，研究以下内容：（1）观察骨癌痛大鼠脊髓中lncRNA NONRATT009773.2表达的时程变化、亚细胞定位；（2）研究其表达变化对骨癌痛行为学的影响；（3）在细胞和动物水平探讨其调控骨癌痛的分子机制。本项目将有望从表观遗传学角度揭示骨癌痛的发生机制，为骨癌痛的治疗寻找新的分子靶点。

Bone cancer pain （BCP）is one of the most common clinical symptoms after cancer patients with bone metastases. Although long-chain noncoding RNA (lncRNA) plays an important role in the occurrence and development of chronic pain, the role of lncRNA at spinal level in BCP has not been reported. Our previous studies found that lncRNA NONRATT009773.2 expression in the spinal cord of rats with BCP increased significantly. Inhibition of lncRNA NONRATT009773.2 alleviated BCP, while miR-708-5p increased and CXCL13 decreased in the spinal cord. Based on this we propose a new hypothesis: lncRNA NONRATT009773.2 regulates BCP through the miR-708-5p / CXCL13 axis. In order to check this hypothesis, this project intends to establish bone cancer pain models and study the following: (1) The expression and cellular distribution of lncRNA NONRATT009773.2 in the spinal cord of BCP rats; (2) The effect of lncRNA NONRATT009773.2 on pain behavior in BCP rats; (3) The molecular mechanism of lncRNA NONRATT009773.2 in regulating bone cancer pain at cell and animal level. This project is expected to reveal the mechanism of BCP from the perspective of epigenetics, and find new molecular targets for the treatment of BCP.