目的:通过CRISPR Screen正向基因筛选技术,筛选出他莫昔芬耐药靶点基因免疫球蛋白结合蛋白1(immunoglobulin binding protein 1,IGBPl).验证IGBP1在临床乳腺癌患者肿瘤组织中是否高表达,并探讨IGBP1对雌激素受体阳性(ER+)乳腺癌细胞增殖、细胞周期和耐药性等表型的影响,为诊断和治疗提供潜在靶点.方法:应用公共数据库分析IGBP1在乳腺癌患者肿瘤组织及配对癌旁组织中的表达是否有所不同.Kaplan-Meier Plotter用于预测1GBP1对乳腺癌患者总体生存率(the overall survival,OS)是否有所影响.应用慢病毒感染ER+乳腺癌细胞,再进行功能实验验证IGBP1过表达及敲低对ER+乳腺癌细胞增殖、细胞周期和耐药性的影响.最后用公共数据库鉴定出可能与IGBP1正、负相关的基因.结果:公共数据库的结果表明,IGBP1在乳腺癌组织中高表达.生存分析表明,IGBP1高表达的患者的OS较差.细胞功能实验显示,过表达IGBP1的细胞增殖、细胞周期明显快于对照组细胞,耐药性增强;而敲低IGBP1的结果相反.与IGBP1正相关的基因里有已知的癌基因如NOP53.结论:IGBP1在ER+乳腺癌中高表达,IGBP1的过表达和敲低均影响ER+乳腺癌细胞系的增殖、细胞周期和耐药性,提示IGBP1在ER+乳腺癌中可能能够改善其耐药,表明IGBP1可能作为ER+乳腺癌的潜在治疗靶点之一.
Effects of IGBP1 on proliferation and tamoxifen resistance in ER-positive breast cancer
Objective:Used CRISPR Screen,a forward gene screening technique,to screen for the tamoxifen-resistant target gene,im-munoglobulin binding protein 1(IGBP1).Then we verified whether IGBP1 was overexpressed in tumor tissues of clinical patients with breast cancer and explored the impact of IGBP1 on cell proliferation,cell cycle,drug resistance,and other phenotypes in patients with estrogen receptor-positive(ER+)breast cancer,with the aim to provide potential targets for the diagnosis and treatment of the disease.Methods:Public databases were used to analyze whether the expression of IGBP1 was different in the tumor tissue and paracancerous tissue of patients with breast cancer.Kaplan Meier Plotter was used to predict the impact of IGBP1 on the overall survival(OS)of patients with breast cancer.The impact of IGBP 1 overexpression and knockdown on cell proliferation,cell cycle,and drug resistance of ER+breast cancer cells was verified using functional experiments following ER+breast cancer cell infection with lentivirus.Finally,public databases were used to identify genes that may be positively or negatively correlated with IGBP 1.Results:The results from the public databases showed that IGBP1 was highly expressed in breast cancer tissue.Survival analysis showed that patients with high expression of IGBP1 had poorer OS.Cell functional experiments showed that cells overexpressing IGBP1 had significantly faster prolif-eration and cell cycle and increased drug resistance than control cells,while the results were opposite for cells with IGBP1 knockdown.There were known oncogenes such as NOP53 among genes that were positively correlated with IGBP1.Conclusion:IGBP 1 is highly expressed in ER+breast cancer.Either overexpression or knockdown of IGBP 1 will affect the proliferation,cell cycle,and drug resis-tance of ER+breast cancer cell lines,suggesting that IGBP1 may improve drug resistance in ER+breast cancer and thus be one of the potential therapeutic targets for ER+breast cancer.
immunoglobulin binding protein 1breast cancerestrogen receptor-positivetamoxifen-resistant
万方数据
维普
