CircFNDC3B调节miR-107/HMGA1轴对胃癌细胞恶性生物学行为的影响  

Effect of CircFNDC3B on the malignant biological behavior of gastric cancer cells by regulating the miR⁃107/HMGA1 axis

作　　者：李雪龙 李志仁 杨妮 LI Xue-ong;LI Zhi-ren;YANG Ni(Department of Gastroenterology,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020,China)

机构地区：[1]首都医科大学附属北京朝阳医院消化科,北京100020

出　　处：《解剖学研究》2024年第3期257-264,271,共9页Anatomy Research

摘　　要：目的探讨环状RNA FNDC3B(CircFNDC3B)调节微小RNA-107/高迁移率家族蛋白A1(miR-107/HMGA1)轴对胃癌(GC)细胞恶性生物学行为的影响。方法体外培养正常胃上皮细胞GES-1和人胃癌细胞系AGS、HCG27、MKN28、BGC-823,RT-qPCR检测CircFNDC3B、miR-107和HMGA1表达,筛选出最佳细胞系。双荧光素酶报告基因实验验证miR-107与CircFNDC3B、HMGA1的靶向关系;选择BGC-823细胞进行转染,将细胞分为si-NC组、si-CircFNDC3B组、si-CircFNDC3B+NC inhibitor、si-CircFNDC3B+miR-107 inhibi-tor组、miR-NC组、miR-107 mimics组、miR-107 mimics+pcDNA、miR-107 mimics+HMGA1组,MTT法检测细胞增殖;Transwell检测细胞迁移和侵袭能力;流式细胞技术检测细胞凋亡;Western blot检测Ki67、Cyclin D1、Bcl-2、cleaved caspase3、E-cadherin、N-cadherin蛋白表达。结果在胃癌细胞系中CircFNDC3B、HMGA1表达显著增加,miR-107表达显著下降(P<0.05);双荧光素酶报告基因实验结果显示,miR-107与CircFNDC3B、HMGA1具有靶向关系;沉默CircFNDC3B表达或过表达miR-107可显著抑制细胞增殖、迁移、侵袭和EMT,促进细胞凋亡(P<0.05);抑制miR-107表达或过表达HMGA1可逆转沉默CircFNDC3B或过表达miR-107对BGC-823细胞增殖、迁移、侵袭和EMT的抑制作用(P<0.05)。结论CircFNDC3B在胃癌细胞中高表达,沉默CircFNDC3B通过调节miR-107/HMGA1轴抑制胃癌细胞恶性生物学行为。Objective To investigate the impact of circular RNA FNDC3B(CircFNDC3B)on the malig⁃nant biological behaviors of gastric cancer(GC)cells by regulating the micro RNA⁃107/high mobility group protein A1(miR⁃107/HMGA1)axis.Methods Normal gastric epithelial cells GES⁃1 and human gastric cancer cell lines AGS,HCG27,MKN28,BGC⁃823 were cultured in vitro,RT⁃qPCR was applied to detect the expression of CircF⁃NDC3B,miR⁃107,and HMGA1,and to screen the optimal cell line.Double Luciferase reporter gene experiment was applied to verify the targeting relationship between miR⁃107 and CircFNDC3B,HMGA1;BGC⁃823 cells were selected for transfection and grouped into si⁃NC group,si⁃CircFNDC3B group,si⁃CircFNDC3B+NC inhibitor,si⁃Cir⁃cFNDC3B+miR⁃107 inhibitor group,miR⁃NC group,miR⁃107 mics group,miR⁃107 mics+pcDNA,and miR⁃107 mics+HMGA1 group,MTT method was applied to detect cell proliferation;Transwell was applied to detect cell mi⁃gration and invasion;flow cytometry was applied to detect cell apoptosis;Western blot was applied to detect the ex⁃pression of Ki67,Cyclin D1,Bcl⁃2,cleaved caspase3,E⁃cadherin,and N⁃cadherin proteins.Results In GC cell lines,the expression of CircFNDC3B and HMGA1 obviously increased,while the expression of miR⁃107 obviously decreased(P<0.05);the results of double luciferase reporter gene experiment showed that miR⁃107 had a targeting relationship with CircFNDC3B and HMGA1;silencing the expression of CircFNDC3B or overexpressing miR⁃107 was able to obviously inhibit cell proliferation,migration,invasion,and EMT,and promote cell apoptosis(P<0.05);inhibiting the expression of miR⁃107 or overexpressing HMGA1 was able to reverse the inhibitory effects of silencing CircFNDC3B or overexpressing miR⁃107 on the proliferation,migration,invasion,and EMT of BGC⁃823 cells(P<0.05).Conclusion CircFNDC3B is highly expressed in GC cells,and silencing CircFNDC3B inhibits the malignant biological behavior of gastric cancer cells by regulating the miR⁃107/HMGA1 axis

关 键 词：胃癌细胞 环状RNA FNDC3B 微小RNA-107/高迁移率家族蛋白A1 恶性生物学行为 

分 类 号：R735.2[医药卫生—肿瘤]