癌相关成纤维细胞来源外泌体介导lncRNA RORA-AS1调控口腔癌放射耐受性的作用及机制研究

肿瘤微环境与肿瘤的放疗耐受性密切相关，但在口腔癌放疗耐受性获得中的作用及分子机制尚不明确。我们前期发现：癌相关成纤维细胞呈天然放射抵抗性，并且与口腔癌细胞共培养后可以促进其细胞放疗耐受性产生，而这一作用是通过癌相关成纤维细胞所释放的外泌体刺激口腔癌细胞中IFITM1表达增高从而激活STAT/p53/p21信号通路完成。我们进一步通过高通量芯片和生信分析筛选出癌相关成纤维细胞和正常成纤维细胞来源外泌体中的差异lncRNA，并预测lncRNA RORA-AS1可调控口腔癌细胞中IFITM1的表达。推测癌相关成纤维细胞来源的外泌体可能介导RORA-AS1来调控IFITM1表达从而影响口腔癌细胞的放疗耐受性。我们拟从临床、体外细胞、动物模型三个层面探讨癌相关成纤维细胞来源exosomal-lncRNA调控口腔癌放射耐受性的作用及分子机制，为口腔癌的放射治疗提供新线索。

The tumor microenvironment is closely related to tumor radiotherapy tolerance. However, its role and molecular mechanism in oral cancer radiotherapy tolerance are not yet understood. Based on our previous study, cancer-associated fibroblasts are naturally radioresistant and co-cultured with oral cancer cells that can promote their resistance to radiotherapy. This effect is due to the exosomes released by cancer-associated fibroblasts stimulate the increase of IFITM1 expression in oral cancer cells, thereby activating the STAT / p53 / p21 signaling pathway. We further screened differential lncRNAs in exosomes derived from cancer-associated fibroblasts and normal fibroblasts via high-throughput microarrays and bioinformatics analysis and predicted that lncRNA RORA-AS1 could regulate the expression of IFITM1 in oral cancer cells. We speculate that cancer-associated fibroblast-derived exosomes may mediate RORA-AS1 to regulate the expression of IFITM1 and thus affect the radiotherapy tolerance of oral cancer cells. We intend to explore the role and molecular mechanism of cancer-related fibroblast-derived exosomal-lncRNA in regulating oral cancer radiation tolerance from three levels: clinical, in vitro cells, and animal models, to provide new clues for radiotherapy of oral cancer.