Cancer Management and Research (Nov 2020)
Ropivacaine Inhibits Cell Proliferation, Migration and Invasion, Whereas Induces Oxidative Stress and Cell Apoptosis by circSCAF11/miR-145-5p Axis in Glioma
Abstract
Danqin Yin,1,* Li Liu,2,* Zhengyuan Shi,1 Lihui Zhang,3 Yan Yang4 1Department of Anesthesiology, Danyang People’s Hospital of Jiangsu, Danyang City, Jiangsu Province, People’s Republic of China; 2Department of Anesthesiology, Tianjin Fourth Central Hospital, Tianjin City, People’s Republic of China; 3Department of Anesthesiology, Hulunbeier Municipal People’s Hospital (Hulunbuir Hospital Affiliated to Suzhou University), Hulunbeier City, Inner Mongolia Province, People’s Republic of China; 4Department of Anesthesiology, The First People’s Hospital of Jiangxia District, Wuhan City, Hubei Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan YangDepartment of Anesthesiology, The First People’s Hospital of Jiangxia District, No. 1 Cultural Avenue, Jiangxia District, Wuhan 430200, Hubei Province, People’s Republic of ChinaTel\Fax +86 13775889005Email [email protected]: Glioma is a heterogeneous aggressive tumor. Ropivacaine, a widely used anesthetic, has been shown to repress the progression of multiple cancers, including glioma. In this study, the effects of ropivacaine on cell proliferation, migration, invasion and apoptosis in glioma were revealed.Methods: The expression levels of circSCAF11 and miR-145-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in glioma tissues and cells. The expression levels of epithelial–mesenchymal transition (EMT)-related proteins were determined by Western blot. Oxidative stress was evaluated by the measurement of reactive oxygen species (ROS) and determination of mitochondrial 8-hydroxy-2-deoxyguanosine (8-OHdG) assay in glioma cells. Cell proliferation was determined by cell counting kit-8 (CCK-8) assay and cell colony formation assay. Cell apoptosis and metastasis were detected by flow cytometry analysis and transwell assay, respectively. The binding relationship between circSCAF11 and miR-145-5p was predicted by circular RNA Interactome and identified by dual-luciferase reporter assay and RNA immunoprecipitation assay. In vivo tumor formation assay was performed to reveal the effects between ropivacaine and circSCAF11 overexpression on tumorigenesis in vivo.Results: CircSCAF11 expression was obviously upregulated and miR-145-5p was significantly downregulated in glioma tissues and cells compared with control groups. Ropivacaine treatment upregulated E-cadherin protein expression and repressed the protein expression of Vimentin. Functionally, ropivacaine exposure promoted ROS and 8-OHdG production and cell apoptosis, whereas inhibited cell proliferation, migration and invasion; however, these effects were hindered by circSCAF11 overexpression. Mechanistically, circSCAF11 was a sponge of miR-145-5p. In addition, ropivacaine was revealed to inhibit tumor growth in vivo by regulating circSCAF11 and miR-145-5p expression.Conclusion: Ropivacaine suppressed glioma progression by regulating circSCAF11 and miR-145-5p, which might provide a theoretical foundation in glioma treatment.Keywords: glioma, ropivacaine, circular RNA, circSCAF11, miR-145-5p
