The effects of etomidate on the proliferation,apoptosis,and invasion of gastric cancer cells by regulating the miR-204-5p/HOXC8 axis
Liu Yan
Li Jun
Zhou Min
Xia Tian
Xia Ganlin
Abstract：Objective To investigate the effects of etomidate(Eto)on the proliferation,apoptosis,and invasion of human gastric cancer cells by regulating the microRNA(miR)-204-5p/homologous box gene C8(HOXC8)axis.Methods Experiments were conducted in the Laboratory of Wuhan University of Science and Technology in April 2023 to April 2024.Gastric cancer cells MKN45 were separated into control(Ctrl)group,low-dose Eto group(Eto-L,5 μmol/L),medium-dose Eto group(Eto-M,10 μmol/L),high-dose Eto group(Eto-H,20 μmol/L),Eto-H+miR inhibitor NC,and Eto-H+miR-204-5p inhibitor group.CCK-8 method and colony formation assay were applied to detect cell proliferation.Flow cytometry was ap-plied to detect apoptosis in MKN45 cells.Transwell assay was applied to detect cell invasion ability.QRT-PCR was applied to detect the mRNA levels of miR-204-5p and HOXC8 in cells.Dual luciferase assay was applied to detect the targeting rela-tionship between miR-204-5p and HOXC8.Results Compared with the control group,the survival rate of MKN45 cells(F/P=33.391/＜0.001),colony formation rate(F/P=29.646/＜0.001),cell invasion rate(F/P=44.814/＜0.001),and HOXC8 mRNA level(F/P=45.485/＜0.001)in Eto-L,Eto-M,and Eto-H groups were greatly lower while the apoptosis rate(F/P=78.091/＜0.001)and miR-204-5p level(F/P=22.665/＜0.001)were greatly higher.Compared with the Eto-H group and Eto-H+miR inhibitor NC group,the survival rate of MKN45 cells(q/P=8.099/＜0.001),colony formation rate(q/P=7.857/＜0.001),cell invasion rate(q/P=7.768/＜0.001),and HOXC8 mRNA level(q/P=11.162/＜0.001)in Eto-H+miR-204-5p inhib-itor group were greatly higher(P＜0.05),while the apoptosis rate(q/P=10254/＜0.001)and miR-204-5p level(q/P=8596/＜0.001)were greatly lower.Compared with co transfected cells with HOXC8-WT and miR-NC,the relative luciferase activity ofMKN45 cells co transfected with HOXC8-WT and miR-204-5p mimic was greatly lower(t/P=5.770/＜0.001).Conclusion Eto may weaken the proliferation and invasion abilities of gastric cancer cells,and promote cell apoptosis by upregulating miR-204-5p and downregulating HOXC8.
Keywords：Gastric cancerEtomidatemicroRNA-204-5p/homologous box gene C8 axisMechanism
Publication Date：2025-01-17
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)