Abstract
Sevoflurane is shown to curtail lung cancer (LC) development. Herein, this research sought to investigate the underlying mechanism of sevoflurane in regard to its repressive effects on LC. Expression levels of microRNA (miR)-153-3p, HIF1α, and KDM2B in LC tissues and cells were determined with qRT-PCR. Following sevoflurane pretreatment and/or ectopic expression and knockdown experiments, the malignant phenotypes, and levels of miR-153-3p, HIF1α, and KDM2B in LC A549 cells were detected using Transwell, scratch, EdU, CCK-8, Western blot, and qRT-PCR assays. Relationship between HIF1α and miR-153-3p was verified with a dual-luciferase reporter assay. The interaction between HIF1α and KDM2B was verified with a ChIP assay. LC tissues and cells presented low miR-153-3p expression and high HIF1α and KDM2B expression. Sevoflurane pretreatment, miR-153-3p upregulation, HIF1α downregulation, or KDM2B downregulation impeded the malignant phenotypes of A549 cells. Sevoflurane pretreatment augmented miR-153-3p expression, while miR-153-3p negatively targeted HIF1α. HIF1α bound to the KDM2B promoter to upregulate KDM2B. HIF1α or KDM2B overexpression counteracted the inhibitory effects of sevoflurane pretreatment on A549 cell malignant behaviors. Sevoflurane decreased HIF1α expression through upregulation of miR-153-3p, thereby reducing KDM2B transcription to restrict the malignant phenotypes of LC A549 cells.
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The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.
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XK conceived the ideas. XK and WZY designed the experiments. XK performed the experiments. XK and WZY analyzed the data. XK provided critical materials. XK and WZY wrote the manuscript. WZY supervised the study. All the authors have read and approved the final version for publication.
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The included patients all signed an informed consent form. This research protocol was ratified by the medical ethics committee of The 334 Affiliated Hospital of Nanchang University (No. SPYYXLL-PJ-2023-KY010).
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Xiong, K., Wu, Z. Sevoflurane Confers Protection Against the Malignant Phenotypes of Lung Cancer Cells via the microRNA-153-3p/HIF1α/KDM2B Axis. Biochem Genet (2023). https://doi.org/10.1007/s10528-023-10607-2
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DOI: https://doi.org/10.1007/s10528-023-10607-2