Publication: Anesthetic propofol suppresses growth and metastasis of lung adenocarcinoma in vitro through downregulating circ-MEMO1-miR-485-3p-NEK4 ceRNA axis
Authors
Chen, Lei ; Wu, Guangyi ; Li, Yongle ; Cai, Qiaoying
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-465
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info:eu-repo/semantics/article
Description
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 circRNAMediator 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 NIMArelated 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 circMEMO1, miR-485-3p, NEK4 was determined by dualluciferase reporter assay and Pearson’s correlation
analysis.
Results. Circ-MEMO1 and NEK4 were highexpressed, 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, circMEMO1 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.
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Citation
Histology and Histopathology Vol. 37, nÂş12 (2022)
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