The novel circular RNA circ-CAMK2A enhances lung adenocarcinoma metastasis by regulating the miR-615-5p/fibronectin 1 pathway

被引:42
作者
Du, Jiahui [1 ]
Zhang, Guangzhao [1 ]
Qiu, Hongli [1 ]
Yu, Haifeng [1 ]
Yuan, Wuying [1 ]
机构
[1] Henan Prov Chest Hosp, Minimally Invas Surg, 1 Weiwu Rd, Zhengzhou 450000, Peoples R China
关键词
Circular RNA; microRNA; Lung adenocarcinoma; Metastasis; Prognosis; CANCER; EXPRESSION; BIOMARKER; PROMOTES;
D O I
10.1186/s11658-019-0198-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: 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). Methods: 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. Results: 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. CircCAMK2A 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. Conclusion: Circ-CAMK2A plays a crucial role in the metastasis of LUAD, at least partially, by regulating the miR-615-5p/fibronectin 1 axis.
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页数:13
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