circRAPGEF5 Contributes to Papillary Thyroid Proliferation and Metastatis by Regulation miR-198/FGFR1
circRAPGEF5 Contributes to Papillary Thyroid Proliferation and Metastatis by Regulation miR-198/FGFR1
复制标题
DOI：
10.1016/j.omtn.2019.01.003
复制
发表时间：
2019-03-01
影响因子：
8.8
通讯作者：
Zhou, Ming
中科院分区：
文献类型：
--
作者：
Liu, Weiwei;Zhao, Ji;Zhou, Ming
环状RNA RAPGEF5(CircRAPGEF5)是由RAPGEF5基因的5个外显子产生的，在乳头状甲状腺癌(PTC)中异常表达。然而，CircRAPGEF5是否在PTC肿瘤的发生中起作用仍不清楚。本研究的目的是探讨CircRAPGEF5在PTC中的作用。结果表明，CircRAPGEF5在PTC组织和细胞系中表达上调。CircRAPGEF5基因敲除在体外抑制细胞的增殖、迁移和侵袭；CircRAPGEF5沉默通过“海绵”miR-198下调成纤维细胞生长因子受体1(FGFR1)的表达，抑制PTC的侵袭性生物学行为。荧光素酶分析证实，CircRAPGEF5与miR-198相互作用，miR-198与FGFR1的3‘非编码区相互作用，下调其表达。异种移植实验证实，CircRAPGEF5基因下调通过促进miR-198的表达抑制了FGFR1介导的肿瘤生长。CircRAPGEF5通过CircRAPGEF5/miR-198/FGFR1轴作为肿瘤促进剂，为PTC的治疗提供了潜在的生物标志物和治疗靶点。
The circular RNA RAPGEF5 (circRAPGEF5) is generated from five exons of the RAPGEF5 gene and abnormal expression in papillary thyroid cancer (PTC). However, whether circRAPGEF5 plays a role in PTC tumorigenesis remains unclear. The aim of the present study was to investigate the role of circRAPGEF5 in PTC. The results showed that circRAPGEF5 was upregulated in PTC tissues and cell lines. circRAPGEF5 knockdown inhibited cell proliferation, migration, and invasion in vitro; and circRAPGEF5 silencing downregulated fibroblast growth factor receptor 1 (FGFR1) expression by "sponging" miR-198, suppressing the aggressive biological behaviors of PTC. Luciferase reporter assays confirmed that circRAPGEF5 interacted with miR-198 and that miR-198 interacted with the 3' UTR of FGFR1 to downregulate its expression. Xenograft experiments confirmed that circRAPGEF5 knockdown suppressed FGFR1-mediated tumor growth by promoting miR-198 expression. circRAPGEF5 acts as a tumor promoter via a novel circRAPGEF5/miR-198/FGFR1 axis, providing a potential biomarker and therapeutic target for the management of PTC.