miR-9靶向抑制XIST促CALHM1 m6A去甲基化：糖尿病性神经痛机制研究

深入探讨糖尿病性神经病理性疼痛(DNP)的机制对糖尿病并发症的防治具有重要意义。我们证实大鼠脊髓背角神经元钙稳态调节蛋白1（CALHM1）高表达可促进DNP的发生，认为深入阐明CALHM1高表达的机制可进一步揭示DNP机理。基于前期发现CALHM1表达与miR-9正相关，结合生物信息学预测，我们认为miR-9可能通过抑制XIST上调ALKBH5水平，从而促进CALHM1 m6A去甲基化而使其表达上调，进而促进DNP的发生。我们将研究DNP患者和DNP大鼠模型m6A的富集情况，ALKBH5的表达情况，以及XIST的表达情况及其定位；研究干预miR-9、ALKBH5、XIST的表达水平对DNP和CALHM1 m6A水平的影响，以明确miR-9、XIST、ALKBH5三者对CALHM1 m6A水平的影响及其与DNP发生之间的关系，为阐明DNP的发生机制提供新理论，为开发特异性镇痛药物提供思路。

It is significant to explore the mechanism of Diabetic neuropathy pain (DNP), then prevent and cure this common complication patients with diabetes mellitus. We identified that overexpression of calcium homeostasis modulator 1 (CALHM1) would promote DNP. Illuminating the mechanism will help us know more about DNP. As we known that overexpression of CALHM1 is positively related to the expression of miR-9. Combined with the bioinfomatic analysis, we hypothesized that miR-9 promotes m6A demethylation and upregulation of CALHM1 by binding with XIST and increasing the expression of ALKBH5, in the end initiates DNP. In this project, we will explore the enrichment of m6A, the expression of ALKBH5 and XIST in DNP patients and rat-models. Researching the effect on the level of m6A of CALHM1 by intervening the expression of miR-9、XIST、ALKBH5. And explaining the relationship among miR-9、XIST、ALKBH5, the level of m6A of CALHM1, and DNP. This project will supply theoretical basis to elucidate the mechanism of DNP and supply experimental data to develop specific analgesics.