circPSD-93调控亲本基因PSD-93转录参与紫杉醇诱导痛觉过敏的机制研究

紫杉醇诱导的痛觉过敏是制约其抗肿瘤疗效的重要原因，但机制不清。研究表明circRNA与神经系统疾病密切相关。然而circRNA在紫杉醇诱导痛觉过敏中的作用，尚不清楚。预实验显示：紫杉醇上调脊髓背角神经元细胞核中circPSD-93表达；而敲低circPSD-93显著抑制痛觉过敏及其亲本基因PSD-93转录。文献显示，hnRNPK/CDK9复合物可通过增强RNA聚合酶II(Pol II)磷酸化，促进转录进程。因而推测：上调的circPSD-93可能通过与hnRNPK/CDK9复合物结合，促进pol II与PSD-93基因结合，增强PSD-93转录，介导痛觉敏化。本项目将：在明确紫杉醇诱导痛觉过敏中circPSD-93功能的基础上，探索circPSD-93通过调控Pol II/hnRNPK/CDK9相互作用增强PSD-93表达，介导痛觉过敏的机制。研究将为阐明紫杉醇诱导痛觉过敏提供新的证据。

Allodynia caused by paclitaxel is an important reason that restricts its anti-tumor efficacy, but the underlying mechanism is not clear now. Studies have shown that circRNA is closely related to neurological diseases. However, the role of circRNA in paclitaxel-induced allodynia remains unclear. Our preliminary experiments found that paclitaxel treatment significantly up-regulated the expression of circPSD-93 in the nucleus of spinal dorsal horn neurons, and inhibited the expression of circPSD-93 significantly reduced allodynia and PSD-93 transcription. Studies have shown that the hnRNPK/CDK9 complex can promote the transcription process by enhancing the phosphorylation of RNA polymerase II (Pol II). Therefore, we hypothesized that the up-regulated circPSD-93 might combine with hnRNPK/CDK9 complex, then promote the binding of pol II and PSD-93 DNA, thereby enhancing the transcriptional expression of the parental gene PSD-93 and inducing allodynia in rats. This project will: on the basis of clarifying the function of circPSD-93 in paclitaxel-induced allodynia, explore the mechanism of circPSD-93 by regulating the interaction of Pol II/hnRNPK/CDK9 to enhance PSD-93 expression and mediating allodynia. This project will provide a new evidence to elucidate paclitaxel-induced allodynia.