环境雌激素壬基酚通过上调miR-151a促进结直肠癌细胞增殖、迁移及侵袭  

Xenoestrogen nonylphenol promotes proliferation,migration,and invasion of colorectal cancer cells by upregulating miR-151a

作　　者：张念杰 张远威 尹硕 万磊 陈旭 王彪 杨雪峰 ZHANG Nianjie;ZHANG Yuanwei;YIN Shuo;WAN Lei;CHEN Xu;WANG Biao;YANG Xuefeng(Department of Gastrointestinal Surgery,the Second Affiliated Hospital of Zunyi Medical University,Guizhou Zunyi 563000,China)

机构地区：[1]遵义医科大学第二附属医院胃肠外科,贵州遵义563000

出　　处：《现代肿瘤医学》2024年第22期4220-4227,共8页Journal of Modern Oncology

基　　金：贵州省科技计划项目(编号:黔科合-ZK[2022]一般631);贵州省卫生健康委科技基金(编号:gzwjkj2020-1-099);遵义医科大学第二附属医院硕士启动基金(编号:SQ-2021-14,SQ-2021-15)。

摘　　要：目的:研究环境雌激素壬基酚(nonylphenol,NP)促进结直肠癌细胞恶性生物学行为及与miR-151a表达的关系。方法:选用HCT-116、COLO205细胞作为实验细胞,EdU及Transwell验证NP对细胞增殖、迁移及侵袭的影响。RNA测序及qPCR分析NP对细胞miR-151a的影响,TCGA分析miR-151a在肠癌中的表达。EdU及Transwell验证NP联合miR-151a过表达或敲减对细胞增殖、迁移及侵袭的影响。生物信息学及双荧光素酶实验验证miR-151a与FRK的靶向关系,TCGA分析FRK在肠癌中的表达,qPCR检测细胞FRK表达,Western blot检测NP联合miR-151a过表达或敲减对细胞FRK、EMT标志物和WNT/β-catenin通路蛋白的影响。结果:与Control组相比,NP显著促进细胞增殖、迁移及侵袭,RNA测序及qPCR分析表明NP显著增加细胞miR-151a表达(P<0.01)。生信分析及双荧光素酶实验证实miR-151a靶向抑制FRK,且miR-151a在肠癌中高表达、FRK低表达。与Control组相比,miR-151a过表达显著促进细胞增殖、迁移及侵袭,miR-151a敲减则抑制(P<0.01)。与NP组相比,NP联合miR-151a过表达显著促进细胞增殖、迁移及侵袭,联合miR-151a敲减则抑制(P<0.01)。与Control组相比,miR-151a过表达和NP处理均显著抑制细胞E-cadherin、FRK蛋白表达,显著促进N-cadherin、Vimentin、WNT3a和β-catenin蛋白表达,miR-151a敲减则结果相反(P<0.01)。与NP组相比,NP联合miR-151a过表达显著抑制细胞E-cadherin、FRK蛋白表达,显著促进N-cadherin、Vimentin、WNT3a和β-catenin蛋白表达,联合miR-151a敲减则结果相反(P<0.01)。结论:NP通过上调miR-151a靶向抑制FRK促进结直肠癌细胞EMT,从而促进细胞的增殖、迁移、侵袭,其分子机制与WNT/β-catenin通路有关。Objective:To investigate the relationship between effects of xenoestrogen nonylphenol(NP)in promoting the malignant biological behavior of colorectal cancer cells and miR-151a expression.Methods:HCT-116 and COLO205 cells were selected as experimental cells.EdU and Transwell assays were used to verify the effects of NP on cell proliferation,migration,and invasion.RNA sequencing and qPCR were conducted to analyze the effect of NP on cellular miR-151a.TCGA analysis was performed to examine miR-151a expression in colorectal cancer.EdU and Transwell assays were employed to verify the effects of NP combined with miR-151a overexpression or knockdown on cell proliferation,migration,and invasion.Bioinformatics and dual-luciferase experiments were conducted to validate the targeting relationship between miR-151a and FRK.TCGA analysis was performed to assess FRK expression in colorectal cancer.qPCR was used to detect cellular FRK expression,while Western blot was employed to assess the effects of NP combined with miR-151a overexpression or knockdown on cellular FRK,EMT markers,and WNT/β-catenin pathway proteins.Results:Compared to the Control group,NP significantly promoted cell proliferation,migration,and invasion.RNA sequencing and qPCR analysis indicated a significant increase in cellular miR-151a expression with NP treatment(P<0.01).Bioinformatics analysis and dual-luciferase experiments confirmed miR-151a targeting inhibition of FRK,with miR-151a exhibiting high expression and FRK showing low expression in colorectal cancer.Compared to the Control group,miR-151a overexpression significantly promoted cell proliferation,migration,and invasion,while miR-151a knockdown inhibited these processes(P<0.01).Compared to the NP group,NP combined with miR-151a overexpression significantly promoted cell proliferation,migration,and invasion,whereas combined miR-151a knockdown exerted inhibitory effects(P<0.01).Compared to the Control group,both miR-151a overexpression and NP treatment significantly inhibited cellular E-cadherin and

关 键 词：结直肠癌 壬基酚 细胞增殖 侵袭及迁移 上皮-间充质转化 miR-151a 

分 类 号：R735.3[医药卫生—肿瘤]