circRNA-miRNA-mRNA信号轴在疾病进程中发挥调控作用（Science,2017），但对靶mRNA正反馈调控上游circRNA研究不足。申请人发现口腔鳞癌（OSCC）恶性进程中circRFWD3吸附miR-27上调其靶基因PPARγ，后者又调控circRFWD3转录。因此，假定：circRFWD3/miR27/PPARγ形成正反馈循环参与OSCC恶性进程。为验证此假说，拟首先在临床队列上验证该正反馈循环相关分子的表达规律及意义；然后采用基因修饰技术检测circRFWD成环机制，并采用RNA互作技术探究该正反馈循环调控机制；继之采用基因改造细胞系检测正反馈循环中非编码RNA的生物学功能；最后采用动物模型评估circRFWD3和miR-27为靶标的干预效果。研究不仅阐明此正反馈循环在OSCC恶变进程中的作用机制及意义，也为circRNA与下游靶分子形成反馈调控的理论提供依据。

The circRNA-miRNA-mRNA signaling axis plays a regulatory role in disease progression (Science, 2017), but there is insufficient research on the positive feedback regulation of target mRNA and the upstream cirRNA. The applicant found earlier that circRFD3 can sponge miR-27 in the malignant process of oral squamous cell carcinoma, miR-27 can target PPAR, which in turn regulates circRFWD3 transcription. Therefore, we hypothesized that there is a circRFWD3/miR-27/PPARγ positive feedback loop in the malignant progress of oral squamous cell carcinoma promotes. For this purpose, firstly verify the expression and significance of the positive feedback loop-related molecules on the clinical cohort; then utilize genetic modification techniques to detect the circularization mechanism of circRFWD, and use RNA interaction techniques to explore regulation mechanism of the positive feedback loop; then adopt genetically modified cell lines to detect the biological function of non-coding RNA in the positive feedback loop; finally employ animal models to evaluate the intervention effects by target circRFWD3 and miR-27. The study not only elucidates the role and mechanism of this positive feedback loop in the malignant process of OSCC, but also provides a basis for the feedback regulation of circRNA and its downstream target molecules.