Matrine Regulates Proliferation, Apoptosis, Cell Cycle, Migration, and Invasion of Non-Small Cell Lung Cancer Cells Through the circFUT8/miR-944/YES1 Axis.

Abstract

BackgroundNon-small cell lung carcinoma (NSCLC) is the major histological subtype of cancer cases. In the present study, we investigated the association between Matrine, an active component of Chinese medicine, and circFUT8 in NSCLC cells.MethodsThe proliferation ability of NSCLC cells was assessed by MTT and colony-forming assays. Flow cytometry assay was performed to show the apoptosis and cell cycle distribution in NSCLC cells. The protein expression levels of Bcl-2, Cleaved Caspase-3 (C-Caspase3), and YES proto-oncogene 1 (YES1) were measured by Western blot assay. Migration and invasion of NSCLC cells were determined by transwell assay. The expression levels of circFUT8, miR-944 and YES1 were quantified by real-time quantitative polymerase chain reaction (RT-qPCR) assay. The interaction relationship between miR-944 and circFUT8 or YES1 was confirmed by dual-luciferase reporter assay. The anti-tumor role of Matrine in vivo was explored by a xenograft experiment.ResultsMatrine functioned as a carcinoma inhibitor by repressing proliferation, cell cycle process, migration, and invasion while inducing apoptosis in NSCLC cells. Importantly, overexpression of circFUT8 counteracted Matrine-induced effects on NSCLC cells. MiR-944, interacted with YES1, was a target of circFUT8. Under Matrine condition, overexpression of circFUT8 increased proliferation, migration, and invasion while inhibited apoptosis, which was abolished by the upregulation of miR-944. Whereas the silencing of YES1 counteracted miR-944 inhibitor-induced effects on NSCLC cells. Eventually, we also confirmed that Matrine impeded NSCLC tumor growth in vivo.ConclusionMatrine regulated proliferation, apoptosis, cell cycle, migration, and invasion of NSCLC cells through the circFUT8/miR-944/YES1 axis, which provided novel information for Matrine in NSCLC.