增强子RNA FGB在结直肠癌肝转移中的作用

Role of enhancer RNA FGB in liver metastasis of colorectal cancer

目的研究增强子RNA(eRNAs)在结直肠癌肝转移中的调控作用,并进一步明确eRNA FGB在结直肠癌肝转移中的作用。方法从美国国家生物技术信息中心(NCBI)数据库下载获得105例原发性结直肠癌GSE178120和283例结直肠癌肝转移GSE15921组织的基因表达图谱,采用WGCNA分析、lasso回归分析、多重Cox回归分析、Pearson相关性分析结合生存分析,明确结直肠癌肝转移的核心eRNA基因。采用CCK8法、克隆形成和transwell法研究eRNA(FGB)基因对细胞增殖、迁移和侵袭性的影响。结果生物信息学分析筛选出2个具有重要预后意义的eRNA(FGB和SLC38A4)(P<0.05),同时FGB(P=0.00423)对比SLC38A4(P=0.01478)的统计学意义更为显著。体外细胞实验结果,明确FGB的过表达可以抑制结直肠细胞系的增殖和克隆形成能力,同时抑制结直肠癌细胞的转移。结论eRNA在结直肠癌肝转移的调控机制中发挥重要作用,FGB参与了结直肠癌肝转移的分子机制调控,这为结直肠癌肝转移的早期诊断和治疗提供了新的研究策略。

Objective To study the regulatory role of enhancer RNA(eRNAs)in liver metastasis of colorectal cancer,and further clarify the role of enhancer RNA FGB in liver metastasis of colorectal cancer.Methods The gene expression profiles of GSE178120 in 105 cases of primary colorectal cancer and GSE15921 in 283 cases of liver metastasis of colorectal cancer were downloaded from the National Center for Biotechnology Information(NCBI)database.WGCNA analysis,Lasso regression analysis,multiple Cox re⁃gression analysis,Pearson correlation analysis and survival analysis were used to identify the core eRNA genes in colorectal cancer liver metastasis.The effects of the eRNA gene(FGB)on cell proliferation,migration and invasiveness were studied using CCK8,clonal formation and transwell methods.Results Bioinformatics analy⁃sis identified two eRNAs(FGB and SLC38A4)with significant prognostic value(P<0.05),where FGB(P=0.00423)showed greater significance than SLC38A4(P=0.01478).Results of in vitro cell experiments demon⁃strated that overexpression of FGB could suppress the proliferation and clonogenesis of colorectal cancer cell lines,as well as inhibit the metastasis of colorectal cancer cells.Conclusions eRNA plays an important role in the regulatory mechanism of liver metastasis in colorectal cancer.Additionally,FGB is involved in the molecu⁃lar regulation of liver metastasis in colorectal cancer.These findings provide a new research strategy for the early diagnosis and treatment of liver metastasis in colorectal cancer.