Peng Xinzhi, Zhu Yue, Lin Shaojian, Yu Weiming, Zhang Cheng, Tan Langping, Long Miaoyun, Luo Dingyuan, Ji Chengcheng
Department of Thyroid Surgery, The Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
Oxid Med Cell Longev. 2022 Mar 11;2022:9974639. doi: 10.1155/2022/9974639. eCollection 2022.
Thyroid cancer is the most common malignancy of the endocrine system, and its outcome remains unsatisfactory. In recent years, circular RNAs (circRNAs) have emerged as crucial regulators in cancers. In the current study, we aimed to investigate whether and how circRNA_0057209 functioned in thyroid cancer. Initial results revealed that circRNA_0057209 and STK4 were both reduced, while miR-183 was up-regulated in thyroid cancer tissues and cells. Experiments including RNA pull-down and RIP assays further identified that upregulation of circRNA_0057209 augmented the expression of STK4, a target gene of miR-183, by competitively-binding to miR-183. Furthermore, functional experiments provided evidence that overexpression of circRNA_0057209 not only inhibited the proliferative, migratory, and invasive properties of thyroid cancer cells while facilitating their apoptosis but also delayed tumor growth. Conversely, upregulation of miR-183 or silencing of STK4 reversed the changes induced by circRNA_0057209. Meanwhile, mechanistic experimentation demonstrated that circRNA_0057209 promoted STK4 expression by sponging miR-183, while STK4 enhanced YAP phosphorylation to mediate the Hippo pathway, thereby suppressing tumor progression. Altogether, our findings indicated that circRNA_0057209 may serve as a competing endogenous RNA of miR-183 to increase STK4 expression, thus inhibiting the development of thyroid cancer.
甲状腺癌是内分泌系统最常见的恶性肿瘤，其治疗效果仍不尽人意。近年来，环状RNA（circRNA）已成为癌症中的关键调节因子。在本研究中，我们旨在探究circRNA_0057209在甲状腺癌中是否发挥作用以及如何发挥作用。初步结果显示，在甲状腺癌组织和细胞中，circRNA_0057209和STK4均降低，而miR-183上调。包括RNA下拉和RIP分析在内的实验进一步证实，circRNA_0057209的上调通过与miR-183竞争性结合，增强了miR-183靶基因STK4的表达。此外，功能实验表明，circRNA_0057209的过表达不仅抑制了甲状腺癌细胞的增殖、迁移和侵袭特性，促进了其凋亡，还延缓了肿瘤生长。相反，miR-183的上调或STK4的沉默逆转了circRNA_0057209诱导的变化。同时，机制实验证明，circRNA_0057209通过吸附miR-183促进STK4表达，而STK4增强YAP磷酸化以介导Hippo通路，从而抑制肿瘤进展。总之，我们的研究结果表明，circRNA_0057209可能作为miR-183的竞争性内源性RNA来增加STK4表达，从而抑制甲状腺癌的发展。
