PRMT5是Ⅱ型蛋白质精氨酸甲基转移酶，可催化组蛋白和非组蛋白的精氨酸甲基化，从而调控基因转录表达和蛋白功能。我们前期研究发现，在口腔白斑与口腔癌组织中PRMT5表达增加且出现亚细胞定位差异，提示PRMT5亚细胞定位迁移与口腔癌前病变演进相关，然而，其作用仍未明确。进一步研究发现，PRMT5可结合NF-κB p65亚单位、促进细胞上皮-间质转化。因此，我们提出以下假设: 在口腔癌前病变演进过程中PRMT5早期在胞核聚集，然后转移至胞浆；PRMT5可通过甲基化胞核、胞浆不同蛋白而调控基因转录表达，促进上皮细胞恶性转化。为此，本项目拟通过体内外、临床研究等多层面分析PRMT5在口腔癌前病变演进中的表达规律和亚细胞定位特点；明确PRMT5亚细胞定位迁移对细胞生物学行为的影响及作用机制；探究以PRMT5为靶点对口腔癌前病变演进的干预作用。旨在为阐明口腔癌前病变癌变机制提供新的重要证据和防治新靶点。

PRMT5 , a type Ⅱ protein arginine methyltransferase, can regulate gene transcription and protein function through catalyzing the arginine methylation of histones and nonhistone proteins. In our preliminary studies, the overexpression and differential subcellular localization of PRMT5 in oral leukoplakia and oral cancer tissues indicated that the subcellular localization of PRMT5 might be related to the development of oral precancerous lesion. However, the associated role of PRMT5 is still unkonwn. Our further study found that PRMT5 could promote the epithelial-mesenchymal transition (EMT) via binding to the p65 subunit of NF-κB. Then, we hypothesize that in the development of oral precancerous lesion, PRMT5 protein might gather in the nucleus at early stage, and then translocate to the cytoplasm. During the carcinogenetic process, PRMT5 could methylate different cytoplasmic and nuclear proteins, and regulate gene transcription, which consequently accelerate the malignant transformation of epithelial cells. Therefore, by means of in vivo,in vitro and clinical study, we set out to investigate the expression pattern and the subcellular localization of PRMT5 in the development of oral precancerous lesion. Furthermore, we try to examine the effect of subcellular translocation of PRMT5 on cell biological behaviors and related mechanisms, and try to determine the interrupting effect on the development of oral precancerous lesion when targeting PRMT5. All those results would give new insights into the mechanisms and provide novel therapeutic target molecules for the carcinogenesis of oral precancerous lesions.