Circular RNAs (circRNAs) are correlated with the occurrence and progression of differentiated thyroid cancer (THCA). However, the regulatory mechanism of circRNAs in differentiated THCA is unclear. In the present study, we analyzed the circRNA microarray dataset (GSE93522) of thyroid tumors and discovered that circRNA HACE1 (circHACE1) was downregulated in differentiated THCA. We detected circHACE1 expression by quantitative real-time polymerase chain reaction (qRT-PCR). Gain-of-function experiments were performed to analyze the biological function of circHACE1 in differentiated THCA cells in vitro. The regulatory mechanism of circHACE1 in differentiated THCA was explored through bioinformatics analysis, dual-luciferase reporter, RIP (RNA immunoprecipitation), and/or RNA pull-down assays. The biological function of circHACE1 in THCA was confirmed by xenograft assay. We verified that circHACE1 was downregulated in differentiated THCA. Also, differentiated THCA patients with low circHACE1 expression were associated with TNM grade, lymphoid node metastasis, tumor size, and poor prognosis. CircHACE1 overexpression decreased xenograft tumor growth in vivo and induced cell cycle arrest, apoptosis, impeded proliferation, migration, and invasion in differentiated THCA cells in vitro. CircHACE1 could function as a microRNA (miR)-346 sponge and regulated Tfcp2L1 (transcription factor CP2 like 1) expression. MiR-346 overexpression offset circHACE1 elevation-mediated effects on malignant behaviors of differentiated THCA cells. Furthermore, Tfcp2L1 silencing counteracted the suppressive impact of miR-346 inhibitor on the malignancy of differentiated THCA cells. In conclusion, circHACE1 adsorbed miR-346 and elevated Tfcp2L1 expression, thus curbing cell malignancy in differentiated THCA, manifesting that circHACE1 might be a target for differentiated THCA treatment.

环状 RNA (circRNA) 与分化型甲状腺癌 (THCA) 的发生和进展相关。然而，circRNAs在分化的THCA中的调控机制尚不清楚。在本研究中，我们分析了甲状腺肿瘤的 circRNA 微阵列数据集（GSE93522），发现 circRNA HACE1（circHACE1）在分化的 THCA 中下调。我们通过定量实时聚合酶链反应 (qRT-PCR) 检测了 circHACE1 的表达。进行功能增益实验以分析circHACE1在体外分化的THCA细胞中的生物学功能. 通过生物信息学分析、双荧光素酶报告基因、RIP（RNA 免疫沉淀）和/或 RNA 下拉分析，探索了 circHACE1 在分化的 THCA 中的调控机制。异种移植试验证实了 circHACE1 在 THCA 中的生物学功能。我们验证了 circHACE1 在分化的 THCA 中被下调。此外，具有低 circHACE1 表达的分化 THCA 患者与 TNM 分级、淋巴结转移、肿瘤大小和预后不良有关。CircHACE1 过表达可降低体内异种移植肿瘤的生长，并在体外诱导分化的 THCA 细胞的细胞周期停滞、凋亡、阻碍增殖、迁移和侵袭. CircHACE1 可以作为 microRNA (miR)-346 海绵发挥作用并调节 Tfcp2L1（转录因子 CP2 样 1）的表达。MiR-346 过表达抵消了 circHACE1 升高介导的对分化 THCA 细胞恶性行为的影响。此外，Tfcp2L1 沉默抵消了 miR-346 抑制剂对分化的 THCA 细胞恶性肿瘤的抑制作用。总之，circHACE1吸附了miR-346并提高了Tfcp2L1的表达，从而抑制了分化THCA中的细胞恶性肿瘤，表明circHACE1可能是分化THCA治疗的靶点。