LncRNA UCA1调控溶质载体SLC22A18拮抗白癜风黑素细胞氧化应激损害的机制研究

抗氧化系统在拮抗白癜风黑素细胞破坏中起重要作用，但机制不清。团队研究发现lncRNA UCA1能激活黑素细胞的抗氧化系统并拮抗氧化应激损伤。在黑素细胞中过表达UCA1后，转录组测序发现溶质载体SLC22A18表达显著下调。最新研究报道抑制SLC22A18表达可增强果蝇的氧化应激耐受。预实验发现下调SLC22A18表达亦能拮抗黑素细胞的氧化应激损伤。提示UCA1可通过下调SLC22A18表达来拮抗黑素细胞的氧化应激损伤。UCA1被报道可招募转录因子调控下游基因的表达。预测分析发现UCA1可能通过招募PCBP1等转录因子调控SLC22A18表达。因此我们提出“UCA1通过抑制SLC22A18的转录表达，激活抗氧化系统，进而拮抗白癜风黑素细胞氧化应激损伤”的假说。本项目拟揭示UCA1调控SLC22A18转录表达来发挥拮抗白癜风黑素细胞氧化应激损伤的作用及机制，有望为白癜风的抗氧化治疗提供新思路。

Antioxidant system plays an important role in antagonizing melanocyte death in vitiligo, but the mechanism is unclear. We have found that lncRNA UCA1 could activate the antioxidant system to antagonize oxidative stress damage of melanocytes. After UCA1 was overexpressed in melanocytes, transcriptome sequencing revealed that solute vector SLC22A18 expression was significantly down-regulated. Recent studies have reported that inhibition of SLC22A18 expression can enhance oxidative stress tolerance in drosophila. Preliminary experiments showed that downregulation of SLC22A18 expression could also antagonize the oxidative stress damage of melanocytes. It is suggested that UCA1 may antagonize the oxidative stress damage of melanocytes by down-regulating the expression of SLC22A18. UCA1 has been reported to recruit transcription factors to regulate downstream gene expression. Predictive analysis showed that UCA1 might regulate SLC22A18 expression through recruitment of transcription factors such as PCBP1. Therefore, we proposed the hypothesis that UCA1 can antagonize the oxidative stress damage of melanocytes in vitiligo by inhibiting the transcriptional expression of SLC22A18 and activating the antioxidant system. This study aims to reveal the role and mechanism of UCA1 regulation of SLC22A18 transcriptional expression to antagonize the oxidative stress damage of vitiligo melanocytes, and is potential for providing a new idea for the antioxidant treatment of vitiligo.