我们在舌鳞癌中发现circRNF13表达下调，且与患者不良预后及癌细胞耐药相关；过表达circRNF13可阻滞细胞周期、促进凋亡和逆转耐药表型。我们还证实circRNF13与RNF13基因的mRNA由相同前体加工而成，且它们的表达呈负相关。利用最新蛋白组学平台获得过表达和敲低circRNF13前后舌鳞癌细胞中差异表达蛋白谱后，结合生物信息学分析，我们提出了如下科学假说：circRNF13可竞争性抑制RNF13这一E3泛素链接酶的mRNA剪接和蛋白表达，也可作为miR-3147的“海绵”解除miR-3147对SUMO2这一SUMO化调节酶的抑制作用，从而通过RNF13和SUMO2催化细胞内重要蛋白的翻译后修饰(泛素化和/或SUMO化)，最终调控细胞周期、凋亡等相关信号通路，影响舌鳞癌的耐药。本项目将通过一系列体内外实验揭示circRNF13的生物学功能并为舌鳞癌的诊疗提供新的分子标记和靶点。

Our previous data demonstrated that the circular RNA circRNF13 was down-regulated in tongue squamous cell carcinoma (TSCC), and low circRNF13 expression was associated with poor prognosis and drug resistance in TSCC; overexpression of circRNF13 in TSCC cells arrested cell cycle progression, induced apoptosis, and reversed drug resistance phenotype. We also confirmed that the circRNF13 and RNF13 mRNA were processed by the same precursor, and their expression was negatively correlated. Using the latest proteomics platform, we obtained differential expression protein profile from TSCC cells before and after overexpression and knockdown of circRNF13. Through further bioinformatics analyses, we proposed the following hypothesis: circRNF13 can competitive inhibit the mRNA splicing and protein expression of the E3 ubiquitin linked enzyme, RNF13, and can function as a miR-3147 sponge to relieve the inhibition of miR-3147 on the SUMOylation enzyme SUMO2, thus circRNF13 catalyzes post-translational modification (ubiquitination and/or SUMOylation) of important proteins through RNF13 and SUMO2 in cells, and finally regulates cell cycle progression, apoptosis and other related signal pathways, and affects the drug resistance of TSCC cells. In the proposed project, we will reveal the biological function of circRNF13 through a series of experiments in vivo and in vitro and provide new molecular markers and targets for the diagnosis and treatment of TSCC.