口腔白斑相关成纤维细胞关键节点lncRNA抑制白念珠菌的作用机制及靶向干预研究

众所周知白念珠菌感染是促进口腔白斑（OLK）癌变的危险因素，但临床常规抗真菌治疗始终存在耐药易复发问题。宿主导向疗法（HDT）是解决该临床问题的重要选择。申请人较早关注重要宿主细胞口腔白斑相关成纤维细胞（OLKAFs），并依据lncRNAs是HDT重要靶标的概念，首次预测获得OLKAFs中有抑制白念珠菌潜力的关键节点lncRNA（FAM7***）及其编码多肽。藉此提出新科学假说：OLKAFs关键节点lncRNA表达异常可致其下游免疫级联反应和编码多肽抵御白念珠菌感染的功能失调，而促进关键lncRNA恢复正常是准确有效实施HDT的关键所在。为验证上述假说，拟联合采用生物信息学和分子细胞生物学技术，研究FAM7***及编码多肽抑制白念珠菌的作用机制，观察靶向干预FAM7***对OLK白念珠菌感染的阻抑效果。本课题为以lncRNAs为靶标的宿主导向抗真菌疗法、消除念珠菌促癌危险因素提供新思路。

It is well known that Candida albicans infection is a risk factor for the malignant transformation of oral leukoplakia (OLK). However, clinical routine application of antifungal treatment always causes drug resistance and recurrence of Candida albicans infection. Host-directed therapy (HDT) has become an important choice to solve this clinical problem. The applicant has been paying close attention to one kind of most important host cells named OLK-associated fibroblasts (OLKAFs). In the light of the concept that long non-coding RNAs (lncRNAs) are important targets for HDT, the research team leading by the applicant successfully predicted for the first time that lncRNA (FAM7***) and its polypeptide in OLKAFs are the key factors to inhibit Candida albicans infection. Based on previous studies, we propose a novel hypothesis: abnormal expression of the key lncRNA in OLKAFs could lead to a downstream immune cascade and dysfunction of its polypeptide, which contributes to suppression of Candida albicans. Therefore, it is a precise and effective way to implement HDT by enhancing the functional restoration of the key lncRNA in OLKAFs. To validate the hypothesis, we will apply bioinformatics and molecular cell biology techniques to study the regulating molecular mechanisms of FAM7*** and its polypeptide for Candida albicans suppression, and explore whether targeting FAM7*** could contribute to suppression of Candida albicans infection in OLK. This study will help to develop a new approach of host-directed antifungal therapy by targeting the lncRNA in fibroblasts, which benefit for the elimination of malignant transformation caused by Candida albicans infection in OLK.