Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xiwu Road, Xi'an, 710004, Shaanxi, China.
J Endocrinol Invest. 2022 Apr;45(4):825-836. doi: 10.1007/s40618-021-01713-2. Epub 2021 Dec 2.
Circular RNAs (circRNAs) have been identified as vital players in tumors, including papillary thyroid carcinoma (PTC). The purpose of this study is to explore the functions of circ_0059354 on PTC development.
Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to examine the levels of circ_0059354, microRNA-766-3p (miR-766-3p) and ADP ribosylation factor guanine nucleotide exchange factor 1 (ARFGEF1). Cell Counting Kit-8 (CCK-8) assay and colony formation assay were proceeded for cell proliferation ability. Transwell assay was conducted for cell migration and invasion. Tube formation assay was employed to examine the angiogenesis ability. Flow cytometry analysis was adopted for cell apoptosis. Western blot assay was conducted for protein levels. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were utilized to verify the relationships among circ_0059354, miR-766-3p and ARFGEF1. The murine xenograft model was constructed to analyze the function of circ_0059354 in vivo.
Circ_0059354 level was abnormally increased in PTC tissues and cells. Functionally, circ_0059354 silencing suppressed cell proliferation, migration, invasion and angiogenesis and facilitated apoptosis in PTC cells. Circ_0059354 was identified to sponge miR-766-3p, which directly targeted ARFGEF1. Moreover, circ_0059354 directly targeted miR-766-3p to positively regulated ARFGEF1 expression. MiR-766-3p inhibition reversed circ_0059354 knockdown-mediated effect of PTC cell malignant behaviors. Overexpression of miR-766-3p restrained the malignant behaviors of PTC cells, whereas ARFGEF1 elevation reversed the effects. Additionally, circ_0059354 deficiency blocked tumor growth in vivo.
Circ_0059354 served as an oncogene in PTC progression through regulating miR-766-3p/ARFGEF1 axis.
环状 RNA（circRNAs）已被确定为肿瘤的重要参与者，包括甲状腺乳头状癌（PTC）。本研究旨在探讨 circ_0059354 在 PTC 发展中的作用。
采用实时定量聚合酶链反应（qRT-PCR）检测 circ_0059354、微小 RNA-766-3p（miR-766-3p）和 ADP 核糖基化因子鸟嘌呤核苷酸交换因子 1（ARFGEF1）的水平。进行细胞计数试剂盒-8（CCK-8）检测和集落形成实验以检测细胞增殖能力。Transwell 实验用于检测细胞迁移和侵袭。管形成实验用于检测血管生成能力。流式细胞术分析用于细胞凋亡。Western blot 实验用于检测蛋白水平。双荧光素酶报告基因实验和 RNA 免疫沉淀（RIP）实验用于验证 circ_0059354、miR-766-3p 和 ARFGEF1 之间的关系。构建了小鼠异种移植模型以在体内分析 circ_0059354 的功能。
circ_0059354 在 PTC 组织和细胞中异常升高。功能上，circ_0059354 沉默抑制了 PTC 细胞的增殖、迁移、侵袭和血管生成，并促进了细胞凋亡。circ_0059354 被鉴定为海绵 miR-766-3p，其直接靶向 ARFGEF1。此外，circ_0059354 直接靶向 miR-766-3p 以正向调节 ARFGEF1 表达。miR-766-3p 抑制逆转了 circ_0059354 敲低介导的 PTC 细胞恶性行为。miR-766-3p 的过表达抑制了 PTC 细胞的恶性行为，而 ARFGEF1 的升高则逆转了这种作用。此外，circ_0059354 的缺失抑制了体内肿瘤的生长。
circ_0059354 通过调节 miR-766-3p/ARFGEF1 轴在 PTC 进展中发挥癌基因作用。
