Department of Oral and Maxillofacial Surgery, Stomatology Medical Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
School of Stomatology of Qingdao University, Qingdao, China.
Aging (Albany NY). 2022 May 16;14(10):4376-4389. doi: 10.18632/aging.204068.
CircRNAs are engaged in the tumorigenesis and progression of oral squamous cancer cells (OSCC). However, the function and underlying mechanism of circRNAs on tumor-associated immunity escape are largely unknown.
We analyzed the expression pattern of has_circ_0069313 in our in-house database and its correlation with OSCC prognosis. Immunohistochemistry was applied to detected PDL1 expression. RNA fluorescence hybridization was applied to detect subcellular location of circRNA. A luciferase activity assay was used to detect the interaction of has_circ_0069313 and miR-325-3p and its downstream target, Foxp3. Exosomes were collected to detect the exosomal circRNAs and co-culture assays were performed to detect the function of exosomal circRNAs on Tregs.
has_circ_0069313 was upregulated in OSCC tissues and predicts poor prognosis. has_circ_0069313 promotes immunity escape through inhibiting miR-325-3p-induced Foxp3 degradation. has_circ_0069313 is an exosomal circRNA and the transfer of has_circ_0069313 to Treg cells promotes the Treg function through maintaining Foxp3 levels.
Our results indicate that has_circ_0069313 induces OSCC immunity escape via the miR-325-3p-Foxp3 axis in both OSCC cells and Treg cells.
CircRNAs 参与口腔鳞状癌细胞（OSCC）的肿瘤发生和进展。然而，circRNAs 对肿瘤相关免疫逃逸的功能和潜在机制在很大程度上尚不清楚。
我们分析了 circRNA 在内库中的表达模式及其与 OSCC 预后的相关性。应用免疫组织化学检测 PDL1 表达。应用 RNA 荧光杂交检测 circRNA 的亚细胞定位。应用荧光素酶活性测定检测 circRNA 与 miR-325-3p 及其下游靶基因 Foxp3 的相互作用。收集外泌体检测外泌体 circRNAs，并进行共培养实验检测外泌体 circRNAs 对 Treg 的功能。
circRNA 在 OSCC 组织中上调，预测预后不良。circRNA 通过抑制 miR-325-3p 诱导的 Foxp3 降解促进免疫逃逸。circRNA 是一种外泌体 circRNA，外泌体 circRNA 向 Treg 细胞的转移通过维持 Foxp3 水平促进 Treg 功能。
我们的研究结果表明，circRNA 通过 OSCC 细胞和 Treg 细胞中的 miR-325-3p-Foxp3 轴诱导 OSCC 免疫逃逸。
