研究表明，循环RNA参与了人类癌症的发生和发展。然而，循环RNA在甲状腺癌中的作用及其在肿瘤发生过程中的贡献尚不清楚。通过RNA测序检测和qRT-PCR验证了甲状腺癌中循环RNA-miRNA-mRNA的表达谱。通过RNase R和actinomycin实验、亚细胞分离和荧光原位杂交等方法验证了circGLIS3的特性。通过创伤愈合、Transwell、3D培养和Western blot等方法检测了circGLIS3和AIF1L的功能。使用RNA免疫沉淀（RIP）、RNA拉降和双荧光素酶报告基因实验验证了circGLIS3及其下游miRNA的靶基因。通过转染miRNA模拟物或靶基因的siRNA进行功能修复实验。最后，使用转移性小鼠模型研究了circGLIS3在 vivo 中的功能。本研究通过RNA测序发现了一种新的循环RNA（has_circ_0007368，命名为circGLIS3）。circGLIS3在甲状腺癌组织和细胞系中下调，并且与甲状腺癌的恶性临床特征呈负相关。功能研究发现，circGLIS3能抑制甲状腺癌细胞的迁移和侵袭，并与上皮间质转化过程相关。在机制上，circGLIS3通过作为miR-146b-3p海绵上调AIF1L基因的表达来抑制甲状腺癌的进展。我们的研究确定了circGLIS3作为甲状腺癌的一种新的肿瘤抑制因子，表明circGLIS3有望作为甲状腺癌的一种有前景的诊断和预后标志物。 © 2023 Springer Nature Switzerland AG.

Studies have shown that circRNA is involved in the occurrence and development of human cancers. However, it remains unclear that the contribution of circRNA in thyroid carcinoma and its role in the process of tumorigenesis.The expression profile of circRNA-miRNA-mRNA in thyroid carcinoma was detected by RNA sequencing and verified by qRT-PCR. The characteristics of circGLIS3 were verified by RNase R and actinomycin assays, subcellular fractionation, and fluorescence in situ hybridization. The functions of circGLIS3 and AIF1L were detected by wound healing, transwell, 3D culture and Western blot. RNA Immunoprecipitation (RIP), RNA pulldown and dual-luciferase reporter assays were used to verify the target genes of circGLIS3 and downstream miRNAs. Functional rescue experiments were performed by transfecting miRNA mimics or siRNA of target genes. Finally, metastatic mouse models were used to investigate circGLIS3 function in vivo.In this study, we discovered a novel circRNA (has_circ_0007368, named as circGLIS3) by RNA sequencing. CircGLIS3 was down-regulated in thyroid carcinoma tissues and cells line, and was negatively associated with malignant clinical features of thyroid carcinoma. Functional studies found that circGLIS3 could inhibit the migration and invasion of thyroid carcinoma cells, and was related to the EMT process. Mechanistically, circGLIS3 can upregulate the expression of the AIF1L gene by acting as a miR-146b-3p sponge to inhibit the progression of thyroid carcinoma.Our study identified circGLIS3 as a novel tumor suppressor in thyroid cancer, indicating the potential of circGLIS3 as a promising diagnostic and prognostic marker for thyroid cancer.© 2023. Springer Nature Switzerland AG.