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The novel circCLK3/miR-320a/FoxM1 axis promotes cervical cancer progression.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2019-12-12 , DOI: 10.1038/s41419-019-2183-z Hanqing Hong 1, 2 , Hai Zhu 1 , Shujun Zhao 1 , Kaili Wang 1 , Nan Zhang 1 , Yun Tian 1 , Yan Li 1 , Yaping Wang 1 , Xiaofeng Lv 1 , Tianxiang Wei 1 , Yan Liu 1 , Suzhen Fan 1 , Yang Liu 3 , Yuan Li 4 , Aojie Cai 5 , Shuo Jin 4 , Qiaohong Qin 1, 2 , Hongyu Li 1, 2
Cell Death & Disease ( IF 8.1 ) Pub Date : 2019-12-12 , DOI: 10.1038/s41419-019-2183-z Hanqing Hong 1, 2 , Hai Zhu 1 , Shujun Zhao 1 , Kaili Wang 1 , Nan Zhang 1 , Yun Tian 1 , Yan Li 1 , Yaping Wang 1 , Xiaofeng Lv 1 , Tianxiang Wei 1 , Yan Liu 1 , Suzhen Fan 1 , Yang Liu 3 , Yuan Li 4 , Aojie Cai 5 , Shuo Jin 4 , Qiaohong Qin 1, 2 , Hongyu Li 1, 2
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As a new class of non-coding RNA, circular RNAs (circRNAs) play crucial roles in the development and progression of various cancers. However, the detailed functions of circRNAs in cervical cancer have seldom been reported. In this study, circRNA sequence was applied to detect the differentially expressed circRNAs between cervical cancer tissues and adjacent normal tissues. The relationships between circCLK3 level with clinicopathological characteristics and prognosis were analyzed. In vitro CCK-8, cell count, cell colony, cell wound healing, transwell migration and invasion, and in vivo tumorigenesis and lung metastasis models were performed to evaluate the functions of circCLK3. The pull-down, RNA immunoprecipitation (RIP), luciferase reporter and rescue assays were employed to clarify the interaction between circCLK3 and miR-320a and the regulation of miR-320a on FoxM1. We found that the level of circCLK3 was remarkably higher in cervical cancer tissues than in adjacent normal tissues, and closely associated with tumor differentiation, FIGO stage and depth of stromal invasion. Down-regulated circCLK3 evidently inhibited cell growth and metastasis of cervical cancer in vitro and in vivo, while up-regulated circCLK3 significantly promoted cell growth and metastasis in vitro and in vivo. The pull-down, luciferase reporter and RIP assays demonstrated that circCLK3 directly bound to and sponge miR-320a. MiR-320a suppressed the expression of FoxM1 through directly binding to 3'UTR of FoxM1 mRNA. In addition, FoxM1 promoted cell proliferation, migration, and invasion of cervical cancer, while miR-320a suppressed cell proliferation, migration, and invasion through suppressing FoxM1, and circCLK3 enhanced cell proliferation, migration and invasion through sponging miR-320a and promoting FoxM1 expression. In summary, circCLK3 may serve as a novel diagnostic biomarker for disease progression and a promising molecular target for early diagnoses and treatments of cervical cancer.
中文翻译：
新型circCLK3 / miR-320a / FoxM1轴可促进子宫颈癌的进展。
作为一类新的非编码RNA，环状RNA（circRNA）在各种癌症的发生和发展中起着至关重要的作用。但是，很少报道circRNA在宫颈癌中的详细功能。在这项研究中，circRNA序列被用于检测宫颈癌组织与邻近正常组织之间差异表达的circRNA。分析了circCLK3水平与临床病理特征和预后的关系。进行体外CCK-8，细胞计数，细胞集落，细胞伤口愈合，穿孔迁移和侵袭以及体内肿瘤发生和肺转移模型以评估circCLK3的功能。下拉RNA免疫沉淀（RIP）荧光素酶报告基因和拯救实验用于阐明circCLK3和miR-320a之间的相互作用以及miR-320a在FoxM1上的调控。我们发现，在宫颈癌组织中，circCLK3的水平显着高于邻近的正常组织，并且与肿瘤分化，FIGO分期和基质浸润深度密切相关。circCLK3的下调明显抑制了宫颈癌在体外和体内的细胞生长和转移，而circCLK3的上调显着促进了体外和体内的细胞生长和转移。下拉荧光素酶报告基因和RIP分析表明circCLK3直接与miR-320a结合并形成海绵。MiR-320a通过直接结合FoxM1 mRNA的3'UTR抑制FoxM1的表达。此外，FoxM1促进细胞增殖，迁移，miR-320a通过抑制FoxM1抑制细胞增殖，迁移和侵袭，而circCLK3通过使miR-320a变海绵并促进FoxM1表达来增强细胞增殖，迁移和侵袭。总之，circCLK3可以作为疾病进展的新型诊断生物标记物，并且可以作为宫颈癌早期诊断和治疗的有希望的分子靶标。
更新日期：2019-12-13
中文翻译：
新型circCLK3 / miR-320a / FoxM1轴可促进子宫颈癌的进展。
作为一类新的非编码RNA，环状RNA（circRNA）在各种癌症的发生和发展中起着至关重要的作用。但是，很少报道circRNA在宫颈癌中的详细功能。在这项研究中，circRNA序列被用于检测宫颈癌组织与邻近正常组织之间差异表达的circRNA。分析了circCLK3水平与临床病理特征和预后的关系。进行体外CCK-8，细胞计数，细胞集落，细胞伤口愈合，穿孔迁移和侵袭以及体内肿瘤发生和肺转移模型以评估circCLK3的功能。下拉RNA免疫沉淀（RIP）荧光素酶报告基因和拯救实验用于阐明circCLK3和miR-320a之间的相互作用以及miR-320a在FoxM1上的调控。我们发现，在宫颈癌组织中，circCLK3的水平显着高于邻近的正常组织，并且与肿瘤分化，FIGO分期和基质浸润深度密切相关。circCLK3的下调明显抑制了宫颈癌在体外和体内的细胞生长和转移，而circCLK3的上调显着促进了体外和体内的细胞生长和转移。下拉荧光素酶报告基因和RIP分析表明circCLK3直接与miR-320a结合并形成海绵。MiR-320a通过直接结合FoxM1 mRNA的3'UTR抑制FoxM1的表达。此外，FoxM1促进细胞增殖，迁移，miR-320a通过抑制FoxM1抑制细胞增殖，迁移和侵袭，而circCLK3通过使miR-320a变海绵并促进FoxM1表达来增强细胞增殖，迁移和侵袭。总之，circCLK3可以作为疾病进展的新型诊断生物标记物，并且可以作为宫颈癌早期诊断和治疗的有希望的分子靶标。
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