LncRNA MIR4435-2HG调节miR-889-3p/FOXK1轴对卵巢癌细胞增殖迁移和侵袭的影响OA
The Effect of LncRNA MIR4435-2HG in Regulating the miR-889-3p/FOXK1 Axis on the Proliferation Migration and Invasion of Ovarian Cancer Cells
目的:探讨 MIR4435-2HG 是否可调控 miR-889-3p/FOXK1 轴影响卵巢癌(OC)细胞增殖、迁移和侵袭.方法:RT-PCR 检测 OC 组织、癌旁组织、卵巢上皮细胞和 OC 细胞中 MIR4435-2HG、miR-889-3p 和 FOXK1 mRNA 的表达水平;验证 miR-889-3p 与 MIR4435-2HG 和 FOXK1 的靶向关系.将 A2780 细胞分为 NC 组、sh-NC 组、sh-MIR4435-2HG 组、miR-NC 组、miR-889-3p mimics 组、sh-MIR4435-2HG+anti-NC 组、sh-MIR4435-2HG+anti-miR-889-3p 组、miR-889-3p mimics+pc-NC 组,miR-889-3p mimics+pc-FOXK1 组;检测 MIR4435-2HG、miR-889-3p 和 FOXK1 mRNA 表达水平、细胞增殖、迁移、侵袭、MMP-9、PD-L1、CyclinD1、FOXK1、E-cadherin、N-cadherin 和 vimentin 蛋白表达水平;体内实验检测沉默 MIR4435-2HG 表达对卵巢癌肿瘤生长的影响.结果:与癌旁组织比较,OC 组织MIR4435-2HG 和 FOXK1 mRNA 表达水平升高,miR-889-3p 表达水平降低(P<0.05);与 IOSE-80 细胞比较,OC 细胞系 MIR4435-2HG 和 FOXK1 mRNA 表达水平升高,miR-889-3p 表达水平降低(P<0.05);与 NC 组和 sh-NC 组比较,sh-MIR4435-2HG 组 A2780 细胞 MIR4435-2HG 和 FOXK1 mRNA 表达水平、细胞活力、划痕愈合率和细胞侵袭数量、MMP-9、N-cadherin、vimentin、PD-L1 和 FOXK1、CyclinD1蛋白表达水平降低,miR-889-3p 表达水平、E-cadherin 蛋白表达水平升高(P<0.05);与 miR-NC 组比较,miR-889-3p mimics 组 A2780 细胞 FOXK1 mRNA 表达水平、细胞活力、划痕愈合率和细胞侵袭数量、MMP-9、N-cadherin、vimentin、PD-L1 和 FOXK1、CyclinD1 蛋白表达水平降低,miR-889-3p 表达水平、E-cadherin 蛋白表达水平升高(P<0.05);下调 miR-889-3p 表达可降低敲低 MIR4435-2HG 表达对A2780 细胞的抑制作用(P<0.05);上调 FOXK1 可减弱过表达 miR-889-3p 对 A2780 细胞的抑制作用(P<0.05).与 sh-NC 组比较,sh-MIR4435-2HG 组裸鼠肿瘤质量、MIR4435-2HG、FOXK1 mRNA 和蛋白表达水平降低,肿瘤体积减小,miR-889-3p 表达水平升高(P<0.05).结论:敲低 MIR4435-2HG 表达可能通过调控 miR-889-3p/FOXK1 轴来抑制 A2780 细胞.
Objective:To investigate whether MIR4435-2HG can regulate the miR-889-3p/FOXK1 ax-is and affect the proliferation,migration,and invasion of ovarian cancer(OC)cells.Methods:RT-PCR was used to detect the expression levels of MIR4435-2HG,miR-889-3p,and FOXK1 mRNA in OC tissues,adja-cent cancer tissues,ovarian epithelial cells,and OC cells.The targeting relationship between miR-889-3p,MIR4435-2HG,and FOXK1 was validated.A2780 cells were assigned into NC group,sh-NC group,sh-MIR4435-2HG group,miR-NC group,miR-889-3p mimics group,sh-MIR4435-2HG+anti-NC group,sh-MIR4435-2HG+anti-miR-889-3p group,miR-889-3p mimics+pc-NC group,and miR-889-3p mimics+pc-FOXK1 group.The expression levels of MIR4435-2HG,miR-889-3p,and FOXK1 mRNA,cell prolifera-tion,migration,invasion,the protein expression levels of MMP-9,PD-L1,CyclinD1,FOXK1,E-cadherin,N-cadherin,and vimentin were measured.In vivo experiments were used to detect the effect of silencing MIR4435-2HG expression on the growth of ovarian tumors.Results:Compared with adjacent cancer tissues,the MIR4435-2HG and FOXK1 mRNA FOXK1 mRNA in OC tissues increased,while miR-889-3p decreased(P<0.05).Compared with IOSE-80 cells,the MIR4435-2HG and FOXK1 mRNA in OC cell line increased,while miR-889-3p decreased(P<0.05).Compared with the NC group and sh-NC group,the sh-MIR4435-2HG group showed decreased MIR4435-2HG and FOXK1 mRNA expression levels,cell viability,scratch heal-ing rate,number of cell invasions,MMP-9,N-cadherin,vimentin,PD-L1,FOXK1,and CyclinD1 protein ex-pression levels in A2780 cells,and increased miR-889-3p and E-cadherin protein expression levels(P<0.05).Compared with the miR-NC group,the miR-889-3p mimics group showed decreased FOXK1 mRNA ex-pression level,cell viability,scratch healing rate,number of cell invasions,MMP-9,N-cadherin,vimentin,PD-L1,FOXK1,and CyclinD1 protein expression levels in A2780 cells,and increased miR-889-3p and E-cad-herin protein expression levels(P<0.05).Downregulation of miR-889-3p expression was able to reduce the inhibitory effect of knocking down MIR4435-2HG expression on A2780 cells(P<0.05).Upregulation of FOXK1 was able to weaken the inhibitory effect of overexpression of miR-889-3p on A2780 cells(P<0.05).Compared with the sh-NC group,the tumor mass of nude mice in the sh-MIR4435-2HG group,MIR4435-2HG,FOXK1 mRNA and protein expression levels were decreased,the tumor volume was reduced,and the ex-pression level of miR-889-3p was increased(P<0.05).Conclusion:Knockdown of MIR4435-2HG expres-sion may inhibit A2780 cells by regulating the miR-889-3p/FOXK1 axis.
王爱芹;罗志中;左卫微;薛书霞
河北省唐山市人民医院妇科,河北 唐山 063000河北省唐山市人民医院妇科,河北 唐山 063000河北省唐山市人民医院妇科,河北 唐山 063000河北省唐山市人民医院妇科,河北 唐山 063000
卵巢癌MIR4435-2HGmiR-889-3p/FOXK1轴增殖迁移侵袭
Ovarian cancerMIR4435-2HGmiR-889-3p/FOXK1 axisProliferationMi-grationInvasion
《河北医学》 2026 (4)
549-558,10
河北省医学科学研究重点课题计划项目,(编号:20181214)
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