Department of Otorhinolaryngology Head and Neck Surgery, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, China.
Department of Neurosurgery, Wuxi Clinical Medical School of Anhui Medical University, 904th Hospital of PLA(Wuxi Taihu Hospital), Wuxi, China.
Bioengineered. 2022 Mar;13(3):7181-7196. doi: 10.1080/21655979.2022.2036304.
Circular RNAs (circRNAs) play vital roles in the development and progression of various diseases. CircRNA coiled-coil domain containing 66 (circ-CCDC66) has been reported to be involved in several cancers, but its biological function and underlying mechanism in papillary thyroid carcinoma (PTC) remain unclear. We detected the relative expression level of circ-CCDC66 in PTC specimens and cell lines using real-time reverse transcription PCR. In addition, EdU assay, transwell assay, and xenograft analysis were performed to measure the effect of circ-CCDC66 on the proliferative, migratory, and invasive capacities of PTC cells. We also investigated the potential mechanism of circ-CCDC66 by bioinformatics analysis, RNA immunoprecipitation, and dual-luciferase reporter assay. We observed that circ-CCDC66 expression was upregulated in PTC specimens and cell lines and was correlated with poor clinical characteristics of PTC patients. Moreover, experiments demonstrated that knockdown of circ-CCDC66 markedly suppressed the proliferative, migratory, and invasive capacities of PTC cells. Mechanistically, miR-129-5p was a target gene of circ-CCDC66 and was downregulated in PTC tissues. LARP1, a downstream target of miR-129-5p, was upregulated in PTC tissues. In addition, we confirmed that inhibition of circ-CCDC66 could repress xenograft tumor growth. Circ-CCDC66 promoted PTC proliferation, migration, invasion, and tumor growth by sponging miR-129-5p and promoting LARP1 expression.
环形 RNA（circRNAs）在各种疾病的发展和进展中发挥着重要作用。已经报道circRNA 卷曲螺旋结构域包含 66（circ-CCDC66）参与了几种癌症，但它在甲状腺乳头状癌（PTC）中的生物学功能和潜在机制仍不清楚。我们使用实时逆转录 PCR 检测 PTC 标本和细胞系中 circ-CCDC66 的相对表达水平。此外，进行 EdU 测定、Transwell 测定和异种移植分析，以测量 circ-CCDC66 对 PTC 细胞增殖、迁移和侵袭能力的影响。我们还通过生物信息学分析、RNA 免疫沉淀和双荧光素酶报告基因测定研究了 circ-CCDC66 的潜在机制。我们观察到 circ-CCDC66 的表达在 PTC 标本和细胞系中上调，并与 PTC 患者的不良临床特征相关。此外，实验表明，circ-CCDC66 的敲低显著抑制了 PTC 细胞的增殖、迁移和侵袭能力。机制上，circ-CCDC66 是 miR-129-5p 的靶基因，在 PTC 组织中下调。miR-129-5p 的下游靶基因 LARP1 在 PTC 组织中上调。此外，我们证实抑制 circ-CCDC66 可以抑制异种移植肿瘤的生长。Circ-CCDC66 通过海绵 miR-129-5p 并促进 LARP1 表达促进 PTC 的增殖、迁移、侵袭和肿瘤生长。
