Isoglycyrrhizin Inhibits Malignant Progression of Lung Adenocarcinoma via hsa_circ_0027107/miR-651-5p/FOXN2 Axis
Objective To explore the functionality and molecular mechanism of circ_0027107 in lung adenocarcinogenesis and the effect of isoliquiritigenin on lung adenocarcinoma via hsa_circ_0027107.Methods Lung adenocarcinoma gene chip was screened for significantly high expression of hsa_circ_0027107,and the expression of hsa_circ_0027107 in plasma of lung adeno-carcinoma patients and healthy people,cancer cells and normal cells was detected by Quantitative Real-time PCR(qRT-PCR),and fluorescence in situ heterogeneity was detected for the expression of hsa_circ_0027107 in lung adenocarcinoma and paracancer tissues.Lung adenocarcinoma cells A549 and H1299 were cultured,and the function of hsa_circ_0027107 in lung ad-enocarcinoma was assessed by using CCK-8 and clone formation to detect cell proliferation ability.Transwell assay was used to detect cell migration and invasive ability,and scratch assay to detect cell migration ability.The function of hsa_circ_0027107 in lung adenocarcinoma was predicted.Through the miRanda and TargetScan database,miR-651-5p in downstream of circ_0027107 was predicted,and miRDB,miRTarBase and TargetScan database to predict miR-651-5p downstream protein FOXN2,dual luciferase gene assay report to determine the interaction between circ_0027107 and miR-651-5p,miR-651-5p and FOXN2 interactions and verified by relevant functional experiments.Results The results of lung adenocarcinoma gene mi-croarray showed that the cyclic RNA hsa_circ_0027107 was significantly differentially expressed,and the results of fluorescence in situ hybridisation showed that the average fluorescence intensity of hsa_circ_0027107 in the tissues of lung adenocarcinoma pa-tients was lower than that of the cancerous tissues,and that of miR-651-5p was higher than that of the cancerous tissues,and that low expression of hsa_circ_0027107 was associated with the low expression of miR-651-5p and FOXN2.0027107 was as-sociated with lymph node metastasis and clinical staging in lung adenocarcinoma patients.Nucleoplasmic separation showed that both hsa_circ_0027107 and miR-651-5p were mainly expressed in the cytoplasm.Overexpression of hsa_circ_0027107 inhibi-ted the proliferation,migration and invasion ability of lung adenocarcinoma cells,whereas overexpression of miR-651-5p re-versed the effects of circ_0027107 on proliferation,migration and invasion of lung adenocarcinoma cells.Meanwhile,it is found that FOXN2 expression was reduced in NCL-H1299 and A549 and knockdown of FOXN2 reversed the effect of miR-651-5p on proliferation,migration and invasion of lung adenocarcinoma cells.In the study,it is found that isoliquiritigenin could signifi-cantly promote the expression of hsa_circ_0027107 and significantly inhibit the proliferation,migration and invasion ability of lung adenocarcinoma cells in vitro,meanwhile,the functional experiments also confirmed that knocking down the expression of hsa_circ_0027107 could rescue isoliquiritigenin inhibiting proliferation,migration and invasion of lung adenocarcinoma cells.Conclu-sion Lung adenocarcinoma tissues,cells and plasma have low expression of hsa_circ_0027107,which inhibits the malignant bio-logical phenotype of tumour by regulating miR-651-5p acting on FOXN2,it may become a potential diagnostic and therapeutic marker for lung adenocarcinoma.Isoglycyrrhizin inhibits malignant progression of lung adenocarcinoma via hsa_circ_0027107.
万方数据
维普
