MiR-125a-5p靶向FGFR1和FGFR3抑制宫颈癌细胞恶性生物学行为的机制研究  

Mechanism of MiR-125a-5p Targeting FGFR1 and FGFR3 to Inhibit the Malignant Biological Behavior of Cervical Cancer Cells

作　　者：尹晓梅 刘蓬[1] 付淼 田文 王莎 刘昊 王东海 YIN Xiaomei;LIU Peng;FU Miao(Baoding No.2 Central Hospital,Hebei Zhuozhou 072750,China)

机构地区：[1]河北省保定市第二中心医院妇产科,河北涿州072750

出　　处：《河北医学》2024年第9期1421-1428,共8页Hebei Medicine

基　　金：河北省保定市科技计划项目,(编号:2241ZF195)。

摘　　要：目的:探讨微小RNA-125a-5p(miR-125a-5p)靶向成纤维细胞生长因子受体(FGFR)1和FGFR3抑制宫颈癌(CC)细胞恶性生物学行为的机制。方法:采用qRT-PCR法检测37例2022年6月至2023年6月期间在我院进行手术的CC患者术中切除的CC组织标本及癌旁组织标本中miR-125a-5p、FGFR1、FGFR3的表达。以CC细胞CaSKi细胞为研究对象,随机分为Control组、NC-mimics组、miR-125a-5p-mimics组、miR-125a-5p-mimics+pcDNA-NC组、miR-125a-5p-mimics+pcDNA-FGFR1组、miR-125a-5p-mimics+pcDNA-FGFR3组;测定各组中miR-125a-5p、FGFR1、FGFR3的表达;MTT法和平板克隆法检测CaSKi细胞增殖;Transwell实验检测CaSKi细胞的迁移、侵袭;流式细胞仪检测CaSKi细胞的凋亡;WB检测CaSKi细胞中FGFR1、FGFR3蛋白的表达;双荧光素酶报告基因实验验证miR-125a-5p与FGFR1、miR-125a-5p与FGFR3的关系。结果:CC组织中miR-125a-5p表达低于癌旁组织,FGFR1、FGFR3表达高于癌旁组织(P<0.05)。miR-125a-5p-mimics组CaSKi细胞中凋亡率、miR-125a-5p表达高于Control组、NC-mimics组,EdU阳性细胞率、OD 490、迁移数、侵袭数、FGFR1 mRNA和蛋白、FGFR3 mRNA和蛋白表达低于Control组、NC-mimics组(P<0.05);与miR-125a-5p-mimics组、miR-125a-5p-mimics+pcDNA-NC组相比,miR-125a-5p-mimics+pcDNA-FGFR1组凋亡率降低,EdU阳性细胞率、OD 490、迁移数、侵袭数、FGFR1 mRNA和蛋白表达升高(P<0.05),miR-125a-5p-mimics+pcDNA-FGFR3组凋亡率降低,EdU阳性细胞率、OD 490、迁移数、侵袭数、FGFR3 mRNA和蛋白表达升高(P<0.05)。miR-125a-5p靶向负调控FGFR1和FGFR3。结论:miR-125a-5p过表达可以抑制CC细胞的恶性生物学行为,其机制可能是靶向FGFR1和FGFR3实现的。Objective:To investigate the mechanism by which microRNA-125a-5p(miR-125a-5p)targets fibroblast growth factor receptor(FGFR)1 and FGFR3 to inhibit the malignant biological behavior of cervical cancer(CC)cells.Methods:The qRT-PCR method was used to detect the expression of miR-125a-5p,FGFR1,and FGFR3 in CC tissue samples and adjacent tissue samples of 37 CC patients who underwent surgery in our hospital from June 2022 to June 2023.CC CaSKi cells were randomly separated into control group,NC-mimics group,miR-125a-5p-mimics group,miR-125a-5p mimics+pcDNA-NC group,miR-125a-5p mimics+pcDNA-FGFR1 group,and miR-125a-5p mimics+pcDNA-FGFR3 group.The expression of miR-125a-5p,FGFR1,and FGFR3 in each group was measured.MTT and plate cloning methods were applied to detect CaSKi cell proliferation.Transwell experiment was conducted to detect the migration and invasion of CaSKi cells.Flow cytometry was used to detect apoptosis of CaSKi cells.WB was applied to detect the expression of FGFR1 and FGFR3 proteins in CaSKi cells.A dual luciferase reporter gene experiment was applied to verify the relationship between miR-125a-5p and FGFR1,and between miR-125a-5p and FGFR3.Results:The expression of miR-125a-5p in CC tissue was lower than that in adjacent cancer tissue,while the expression of FGFR1 and FGFR3 was higher than that in adjacent cancer tissue(P<0.05).The apoptosis rate and miR-125a-5p expression in CaSKi cells in the miR-125a-5p-mimics group were higher than those in the control group and NC-mimics group,the EdU positive cell rate,OD 490,migration number,invasion number,FGFR1 mRNA and protein,and FGFR3 mRNA and protein expression were lower than those in the control group and NC-mimics group(P<0.05).Compared with the miR-125a-5p-mimics group and the miR-125a-5p mimics+pcDNA-NC group,the apoptosis rate of the miR-125a-5p mimics+pcDNA-FGFR1 group decreased,the EdU positive cell rate,OD 490,migration number,invasion number,FGFR1 mRNA and protein expression increased(P<0.05),the apoptosis rate of the miR-125a-5p mimics+pcDNA-F

关 键 词：微小RNA-125a-5p 成纤维细胞生长因子受体1 成纤维细胞生长因子受体3 宫颈癌 细胞恶性生物学行为 

分 类 号：R737.33[医药卫生—肿瘤]