口腔癌通常对放疗抵抗并导致肿瘤转移与复发，肿瘤干细胞是导致放疗抵抗的主要原因。我们早期研究显示ZNF703与口腔癌细胞的增殖和侵袭转移等生物行为密切相关，但ZNF703能否影响口腔癌干细胞活性，未见报道。本项目前期研究发现ZNF703可调控口腔癌干细胞的活性，并可以负性调控miR-145的表达。通过相关预测软件，我们发现c-Met，可能是miR-145的作用靶基因。在此基础上，我们提出“ZNF703可能通过miR-145/c-Met这一信号通路，影响口腔癌干细胞的活性，进而导致口腔癌细胞的放疗抵抗性”这一假说。同时检测口腔癌标本中ZNF703、miR-145及c-Met表达情况，分析其表达相关性以及与接受放疗预后之间的关系，确定其临床意义。本项目对于探索口腔癌放疗抵抗性的机制以及开发新的放疗增敏剂具有重要意义。

Oral cancer is usually resistant to radiotherapy and may contribute to tumor metastasis and tumor recurrence after treatment.Cancer stem cells (CSCs) are the main cause of radiotherapy resistance.It is well known that ZNF703 is related to proliferation and metastasis of oral cancer cells,however, the effect and mechanism of cancer stem cell activity induced by ZNF703 are still unknown.We found that ZNF703 can regulate the activity of oral cancer stem cells and negatively regulate miR-145 expression.We found that c-Met may be a direct target of miR-145 through the correlation prediction software. Based on the above findings,we hopythesized that ZNF703 may regulate miR-145/ c-Met signaling pathway,thereby affect the activity of oral cancer stem cells and lead to radiotherapy resistance of oral cancer cells.Moreover,we will aslo detect the expression of ZNF703, miR-145 and c-Met in oral cancer specimens by Immunohistochemistry and miRNA in situ hybridization and analyze the relationship between the expression and the prognosis of radiotherapy,thereby identifying the clinical implications.This program will provide new understanding for exploring the mechanism of radiotherapy resistance in oral cancer, and provide new theoretical and experimental basis for the development of new radiotherapy sensitizers.