Prx1/DIRAS2抑制口腔白斑细胞自噬的分子机制研究

氧化应激是影响口腔白斑（OLK）发生发展的重要因素，尤其氧化应激诱导的细胞自噬作用关键，其分子机制值得探讨。过氧化物还原酶1（Prx1）是特异性巯基类抗氧化蛋白，通过清除细胞内的H2O2, 参与氧化应激反应，与细胞恶性转化密切相关。课题组前期研究发现氧化应激诱导Prx1在OLK组织表达增高，上调的Prx1通过结合小G蛋白DIRAS2并影响DIRAS2表达，进一步参与自噬信号通路调控，从而促进OLK的发生发展，目前其具体机制不明，相关研究未见报道。本项目拟利用体外细胞和小鼠癌前病变模型并结合临床口腔白斑标本作为研究对象，在明确Prx1/DIRAS2表达与细胞自噬在OLK发生发展中的作用及其临床意义的前提下，进一步阐释Prx1/DIRAS2信号通路调控细胞自噬在OLK发生发展中的生物学作用及其机制，本研究有助于进一步了解OLK的发生发展规律，从而为临床口腔白斑的针对性治疗提供新的思路。

Oxidative stress is an important factor affecting the occurrence and development of oral leukoplakia (OLK), especially the key role of autophagy induced by oxidative stress, and its molecular mechanism is worth exploring. Peroxiredoxin 1 (Prx1) is an antioxidant protein, which is involved in oxidative stress reaction by scavenging H2O2 in cells, and is also closely related to malignant transformation of cells. Our previous study found that oxidative stress induced increased expression of Prx1 in OLK tissues, and the upregulated Prx1, in turn, affected the expression of a small G protein DIRAS2 by binding to DIRAS2, further participated in the regulation of autophagy signaling pathway, thereby promoting the occurrence and development of OLK. Currently, the specific mechanism is unknown, and relevant studies have not been reported. We will investigate cell in vitro and mouse models of precancerous lesions combined with clinical oral leukoplakia specimens in this study. The purpose of this study: 1) to clarify the role and clinical significance of Prx1/DIRAS2 expression and autophagy in the development and progression of OLK, 2) to elucidate the biological role and mechanism of Prx1/DIRAS2 signaling pathway in the regulation of autophagy in the development and progression of OLK. Our results are of practical significance to understand the occurrence and development of OLK and to adopt effective targeted treatment of OLK.