Anesthetic propofol suppresses growth and metastasis of lung adenocarcinoma in vitro through downregulating circ-MEMO1-miR-485-3p-NEK4 ceRNA axis

Abstract

Background: Recently, circular RNAs (circRNAs) have been emerging as new regulators in the propofol-induced tumor-suppressive role. Here, we intended to investigate the involvement of circRNA-Mediator of cell motility 1 (circ-MEMO1; hsa_circ_0007385) in propofol role in cancer hallmarks of lung adenocarcinoma (LUAD).

Methods: Real-time quantitative PCR and western blotting examined transcriptional and translational levels of circ-MEMO1, microRNA (miR)-485-3p, and NIMA-related kinase-4 (NEK4), and markers of growth and metastasis including E-cadherin, CyclinD1, and Vimentin. Cancer hallmarks were measured by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, 5-ethynyl-2-deoxyuridine assay, and transwell assay. The interaction among circ-MEMO1, miR-485-3p, NEK4 was determined by dual-luciferase reporter assay and Pearson's correlation analysis.

Results: Circ-MEMO1 and NEK4 were high-expressed, and miR-485-3p was low-expressed in LUAD patients and cells; moreover, circ-MEMO1 and NEK4 expression in LUAD cells could be suppressed, whereas miR-485-3p could be elevated with propofol anesthesia. Functionally, propofol restrained cell viability, cell cycle entrance, cell proliferation, migration, and invasion of LUAD cells, accompanied by promoted E-cadherin and depressed CyclinD1 and Vimentin. Coincidently, high circ-MEMO1 was associated with low overall survival of LUAD patients, and overexpressing circ-MEMO1 could overall attenuate propofol effects in LUAD cells. Of note, upregulating miR-485-3p and/or interfering NEK4 could partially countermand the adverse impacts of circ-MEMO1 on propofol's role in LUAD cells. Importantly, circ-MEMO1 acted as a sponge for miR-485-3p to modulate the expression of miR-485-3p-targeted oncogene NEK4.

Conclusion: Promoting the circ-MEMO1-miR-485-3p-NEK4 axis might halt the tumor-inhibiting role of propofol in LUAD cells in vitro, suggesting a potential epigenetic pathway of propofol.