Hsa_circ_0006692 Promotes Lung Cancer Progression via miR-205-5p/CDK19 Axis

Abstract

Circular RNA (CircRNA) is related to tumor development. Nevertheless, the regulation and function of hsa_circ_0006692 and its interactions with miR-205-5p and CDK19 in the development of non-small-cell lung cancer (NSCLC) were un-explored. The correlations of expression levels of hsa_circ_0006692 in NSCLC specimens and cells with pathological characteristics were studied. The interactions of hsa_circ_0006692 with miR-205-5p and CDK19 were assessed with real-time PCR, RNA-binding protein immunoprecipitation (RIP), luciferase reporter, RNA pull-down, and fluorescence in situ hybridization (FISH). The roles of hsa_circ_0006692 on cell growth, invasion, and migration in vitro and metastasis in vivo were evaluated. Hsa_circ_0006692 was over-expressed in 60 cases of NSCLC specimens and cells, which was positively correlated with TNM stage, tumor size, and invasion of the lung basal layer. The results of the in vitro and in vivo studies revealed that the over-expression of hsa_circ_0006692 facilitated NSCLC cell growth, migration, and invasion, cell cycle arrest at the S phase, and the activation of BCL-2, CCND1, and PCNA. The results of the dual-luciferase reporter assay, RNA immunoprecipitation, and pull-down assays indicated that hsa_circ_0006692 sponged miR-205-5p, which targeted CDK19 and facilitated the malignant behaviors of lung cancer cells. Hsa_circ_0006692 modulated EMT of lung cancer cells via the stimulation of CDH1, CDH2, VIMENTIN, and MMP7. This study revealed that hsa_circ_0006692 promoted NSCLC progression via enhancing cell growth, invasion, and metastasis through sponging mir-205-5p, up-regulating the downstream oncogene CDK19 and modulating EMT of lung cancer cells. The circ-0006692/mir-205-5p/CDK19 axis might serve as a prognosis biomarker and target for drugs aimed against NSCLC.