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The novel circular RNA circ-CAMK2A enhances lung adenocarcinoma metastasis by regulating the miR-615-5p/fibronectin 1 pathway
Cellular & Molecular Biology Letters ( IF 9.2 ) Pub Date : 2019-12-26 , DOI: 10.1186/s11658-019-0198-1
Jiahui Du 1 , Guangzhao Zhang 1 , Hongli Qiu 1 , Haifeng Yu 1 , Wuying Yuan 1
Affiliation  

Circular RNA (circRNA) has recently been considered as a key regulator in carcinogenesis. In this study, we investigated the functional significance and regulatory role of circ-CAMK2A (hsa_circ_0128332) in lung adenocarcinoma (LUAD). GSE101586 was employed to screen differentially expressed circRNAs. = Relative expression levels of circ-CAMK2A, miR-615-5p, fibronectin 1 (FN1), MMP2, and MMP9 were tested by quantitative reverse transcription PCR (qRT-PCR) or western blotting. Functional experiments were performed by CCK-8, wound healing, and transwell assays. Luciferase reporter and biotin-labeled RNA pull-down assays were carried out to evaluate the interaction between circ-CAMK2A, miR-615-5p, and fibronectin 1. In addition, a lung metastasis model was constructed to determine the metastasis-promoting role of circ-CAMK2A in vivo. Circ-CAMK2A overexpression was observed in LUAD and was closely associated with lymph node metastasis, distant metastasis, advanced clinical stage, and poor prognosis. Circ-CAMK2A silencing evidently inhibited LUAD cell migration and invasion, whereas circ-CAMK2A overexpression had an opposite effect. Importantly, overexpression of circ-CAMK2A also enhanced LUAD metastasis in vivo. Mechanistically, miR-615-5p was identified as a direct target of circ-CAMK2A. Circ-CAMK2A up-regulates the expression level of fibronectin 1 by sponging miR-615-5p, thereby increasing MMP2 and MMP9 expression to promote the metastasis of LUAD. Circ-CAMK2A plays a crucial role in the metastasis of LUAD, at least partially, by regulating the miR-615-5p/fibronectin 1 axis.

中文翻译:

新型环状 RNA circ-CAMK2A 通过调节 miR-615-5p/纤连蛋白 1 通路增强肺腺癌转移

环状 RNA (circRNA) 最近被认为是致癌作用的关键调节因子。在这项研究中,我们研究了 circ-CAMK2A (hsa_circ_0128332) 在肺腺癌 (LUAD) 中的功能意义和调节作用。GSE101586 用于筛选差异表达的 circRNA。= 通过定量逆转录 PCR (qRT-PCR) 或蛋白质印迹测试 circ-CAMK2A、miR-615-5p、纤连蛋白 1 (FN1)、MMP2 和 MMP9 的相对表达水平。通过 CCK-8、伤口愈合和 transwell 测定进行功能实验。进行荧光素酶报告基因和生物素标记的 RNA pull-down 测定以评估 circ-CAMK2A、miR-615-5p 和纤连蛋白 1 之间的相互作用。此外,构建肺转移模型以确定促进转移的作用。体内 circ-CAMK2A。在LUAD中观察到Circ-CAMK2A过表达,与淋巴结转移、远处转移、晚期临床分期和预后不良密切相关。Circ-CAMK2A 沉默明显抑制 LUAD 细胞迁移和侵袭,而 circ-CAMK2A 过表达具有相反的作用。重要的是,circ-CAMK2A 的过表达也增强了体内 LUAD 转移。从机制上讲,miR-615-5p 被鉴定为 circ-CAMK2A 的直接靶标。Circ-CAMK2A 通过海绵化 miR-615-5p 上调纤连蛋白 1 的表达水平,从而增加 MMP2 和 MMP9 的表达,促进 LUAD 的转移。Circ-CAMK2A 至少部分通过调节 miR-615-5p/纤连蛋白 1 轴在 LUAD 的转移中起关键作用。远处转移,临床分期晚期,预后差。Circ-CAMK2A 沉默明显抑制 LUAD 细胞迁移和侵袭,而 circ-CAMK2A 过表达具有相反的作用。重要的是,circ-CAMK2A 的过表达也增强了体内 LUAD 转移。从机制上讲,miR-615-5p 被鉴定为 circ-CAMK2A 的直接靶标。Circ-CAMK2A 通过海绵化 miR-615-5p 上调纤连蛋白 1 的表达水平,从而增加 MMP2 和 MMP9 的表达,促进 LUAD 的转移。Circ-CAMK2A 至少部分通过调节 miR-615-5p/纤连蛋白 1 轴在 LUAD 的转移中起关键作用。远处转移,临床分期晚期,预后差。Circ-CAMK2A 沉默明显抑制 LUAD 细胞迁移和侵袭,而 circ-CAMK2A 过表达具有相反的作用。重要的是,circ-CAMK2A 的过表达也增强了体内 LUAD 转移。从机制上讲,miR-615-5p 被鉴定为 circ-CAMK2A 的直接靶标。Circ-CAMK2A 通过海绵化 miR-615-5p 上调纤连蛋白 1 的表达水平,从而增加 MMP2 和 MMP9 的表达,促进 LUAD 的转移。Circ-CAMK2A 至少部分通过调节 miR-615-5p/纤连蛋白 1 轴在 LUAD 的转移中起关键作用。circ-CAMK2A 的过表达也增强了体内 LUAD 转移。从机制上讲,miR-615-5p 被鉴定为 circ-CAMK2A 的直接靶标。Circ-CAMK2A 通过海绵化 miR-615-5p 上调纤连蛋白 1 的表达水平,从而增加 MMP2 和 MMP9 的表达,促进 LUAD 的转移。Circ-CAMK2A 至少部分通过调节 miR-615-5p/纤连蛋白 1 轴在 LUAD 的转移中起关键作用。circ-CAMK2A 的过表达也增强了体内 LUAD 转移。从机制上讲,miR-615-5p 被鉴定为 circ-CAMK2A 的直接靶标。Circ-CAMK2A 通过海绵化 miR-615-5p 上调纤连蛋白 1 的表达水平,从而增加 MMP2 和 MMP9 的表达,促进 LUAD 的转移。Circ-CAMK2A 至少部分通过调节 miR-615-5p/纤连蛋白 1 轴在 LUAD 的转移中起关键作用。
更新日期:2019-12-26
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