七氟醚通过调控Circ_0000423/miR-525-5p/SGPP1网络抑制结直肠癌的增殖、迁移和侵袭。
Sevoflurane Suppresses the Proliferation, Migration and Invasion of Colorectal Cancer Through Regulating Circ_0000423/miR-525-5p/SGPP1 Network.
作者信息
Kang Xiaofang, Li Xiaocong, Li Yanli
机构信息
Department of Anesthesiology, The 980 Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, No. 398, Zhongshan West Road, Shijiazhuang City, 050000 Hebei Province China.
出版信息
Cell Mol Bioeng. 2022 Jan 22;15(2):219-230. doi: 10.1007/s12195-021-00717-5. eCollection 2022 Apr.
INTRODUCTION
Sevoflurane (SEV) has been shown to inhibit the malignant progression in many cancers, including colorectal cancer (CRC). However, it is not clear whether SEV regulates the progression of CRC by mediating the circular RNA (circRNA) axis.
METHODS
Different concentrations of SEV were used to treat CRC cells. Cell proliferation, migration and invasion were determined by cell counting kit 8 assay, colony formation assay and transwell assay. The expression of circ_0000423, microRNA (miR)-525-5p and sphingosine-1-phosphate phosphatase 1 (SGPP1) mRNA was measured by quantitative real-time PCR. Cell apoptosis was assessed using flow cytometry, and protein expression was measured by western blot analysis. Dual-luciferase reporter assay and RIP assay were performed to confirm the interactions among circ_0000423, miR-525-5p and SGPP1. Animal experiments were performed to explore the effect of SEV and circ_0000423 on CRC tumorigenesis.
RESULTS
SEV could inhibit CRC cell proliferation, migration and invasion. Circ_0000423 was upregulated in CRC and its expression could be reduced by SEV. Overexpressed circ_0000423 reversed the inhibitory effect of SEV on CRC cell proliferation, migration and invasion and the promotion effect on cell apoptosis. MiR-525-5p could be sponged by circ_0000423, and its overexpression also abolished the regulation of circ_0000423 on the progression of SEV-treated CRC cells. In addition, SGPP1 was confirmed to be a target of miR-525-5p, and its expression was positively regulated by circ_0000423. MiR-525-5p inhibitor promoted CRC cell progression under the treatment of SEV, while these effects could be overturned by SGPP1 silencing. Furthermore, the inhibition effect of SEV on CRC tumorigenesis also could be abolished by overexpressing circ_0000423.
CONCLUSION
Our results showed that SEV inhibited CRC progression through the regulation of circ_0000423/miR-525-5p/SGPP1 axis.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12195-021-00717-5.
引言
七氟醚（SEV）已被证明可抑制包括结直肠癌（CRC）在内的多种癌症的恶性进展。然而，尚不清楚SEV是否通过介导环状RNA（circRNA）轴来调节CRC的进展。
方法
使用不同浓度的SEV处理CRC细胞。通过细胞计数试剂盒8检测、集落形成检测和Transwell检测来测定细胞增殖、迁移和侵袭。通过定量实时PCR测定circ_0000423、微小RNA（miR）-525-5p和鞘氨醇-1-磷酸磷酸酶1（SGPP1）mRNA的表达。使用流式细胞术评估细胞凋亡，并通过蛋白质印迹分析测定蛋白质表达。进行双荧光素酶报告基因检测和RNA免疫沉淀检测以确认circ_0000423、miR-525-5p和SGPP1之间的相互作用。进行动物实验以探究SEV和circ_0000423对CRC肿瘤发生的影响。
结果
SEV可抑制CRC细胞的增殖、迁移和侵袭。Circ_0000423在CRC中上调，其表达可被SEV降低。过表达的circ_0000423逆转了SEV对CRC细胞增殖、迁移和侵袭的抑制作用以及对细胞凋亡的促进作用。MiR-525-5p可被circ_0000423吸附，其过表达也消除了circ_0000423对SEV处理的CRC细胞进展的调节作用。此外，SGPP1被证实是miR-525-5p的靶标，其表达受circ_0000423正调控。MiR-525-5p抑制剂在SEV处理下促进CRC细胞进展，而这些作用可被SGPP1沉默所逆转。此外，过表达circ_0000423也可消除SEV对CRC肿瘤发生的抑制作用。
结论
我们的结果表明，SEV通过调节circ_0000423/miR-525-5p/SGPP1轴抑制CRC进展。
补充信息
在线版本包含可在10.1007/s12195-021-00717-5获取的补充材料。
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