circ_0072088 通过调控 miR-532-3p/WEE1 轴促进甲状腺癌 IHH4 细胞 的恶性生物学行为

目的：探讨circ_0072088对甲状腺癌IHH4细胞恶性生物学行为的影响及其可能的机制。方法：选取2015年4月至 2019年3月于青海大学附属医院就诊的确诊为甲状腺癌后接受切除手术且术前未进行任何治疗的48例甲状腺癌患者的甲 状腺癌组织及其对应癌旁组织。根据GEO数据集（GSE93522）分析鉴定甲状腺乳头状癌中差异表达的circRNA。用qPCR法检 测circ_0072088在甲状腺癌组织和细胞中的表达水平。采用CCK-8法和Transwell法检测circ_0072088和miR-532-3p过表达对 甲状腺癌IHH4细胞增殖、迁移和侵袭的影响。采用生物信息学和双荧光素酶报告基因实验验证甲状腺癌细胞中circ_0072088与 miR-532-3p、miR-532-3p和WEE1基因之间的关系。结果：circ_0072088在甲状腺癌组织和细胞中呈高表达（P<0.05或P<0.01）。circ_0072088过表达促进了甲状腺癌细胞的增殖、迁移和侵袭（P<0.05或P<0.01），而转染 miR-532-3p 模拟物能够减弱这种 作用（P <0.05或P<0.01）。此外，机制研究表明，circ_0072088可以与miR-532-3p靶向结合，且WEE1是miR-532-3p的下游靶基 因。结论：circ_0072088通过调控miR-532-3p/WEE1轴促进IHH4细胞的增殖、迁移和侵袭。

circ_0072088 promotes the malignant biological behaviors of thyroid cancer IHH4 cells by regulating the miR-532-3p/WEE1 axis

Objective: To explore the effect of circ_0072088 on the malignant biological behaviors of thyroid cancer IHH4 cells and its possible mechanism. Method: From April 2015 to March 2019, the thyroid cancer tissues and corresponding adjacent tissues from 48 patients who were diagnosed as thyroid cancer and underwent resection without any previous treatment in the Affiliated Hospital of Qinghai University were collected. The differentially expressed circRNAs in papillary thyroid cancer were identified by GEO database (GSE93522). The expression pattern of circ_0072088 was determined using quantitative real-time polymerase chain reaction (qRT-PCR) in thyroid cancer samples and cell lines. CCK-8 and Transwell assays were performed to assess the effects of circ_0072088 and miR-532-3p on proliferation, migration, and invasion of thyroid cancer IHH4 cells. Bioinformatics analysis and dual-luciferase reporter assays were used to explore the correlation between circ_0072088 and miR-532-3p as well as between miR-532-3p and WEE1 gene in thyroid cancer cells. Results: circ_0072088 expression was upregulated in thyroid cancer tissues and cell lines ( P<0.05 or P<0.01). Overexpression of circ_0072088 promoted the proliferation, migration, and invasion of thyroid cancer cells (P<0.05 or P<0.01), while transfection of miR-532-3p mimics weakened this effect (P<0.05 or P<0.01). Mechanistically, circ_0072088 could bind to miR-532-3p. Besides, WEE1 was proved to be the downstream target gene of miR-532-3p. Conclusion: Circ_0072088 promotes the proliferation, migration and invasion of IHH4 cells through regulating WEE1/miR-532-3p axis.