ST6GAL2表达下调促进结肠癌细胞生长和转移的多维度研究  

Downregulation of ST6GAL2 expression promotes colon cancer cell growth and metastasis:a multidimensional study

作　　者：程玉 顾晋[1,2] Cheng Yu;Gu Jin(Gastrointestinal Oncology Center,Peking University Cancer Hospital,Beijing 100142,China;Department of Gastrointestinal Surgery,Peking University Shougang Hospital,Beijing 100144,China)

机构地区：[1]北京大学肿瘤医院胃肠肿瘤中心,北京100142 [2]北京大学首钢医院胃肠外科,北京100144

出　　处：《中华临床医师杂志(电子版)》2024年第11期1019-1029,共11页Chinese Journal of Clinicians(Electronic Edition)

基　　金：国家自然科学基金(资助编号:82073223)

摘　　要：目的探讨ST6β-半乳糖苷α-2,6-唾液酸转移酶2(ST6GAL2)对结肠癌细胞生长和转移的影响。方法从生物信息学-组织学-细胞学层面研究ST6GAL2对结肠癌细胞生长和转移的影响。分析TCGA和GEO数据库中ST6GAL2在结直肠癌中的表达,Kaplan-Meier方法评估ST6GAL2的表达高低与总生存期的关系。免疫组化技术验证ST6GAL2在结直肠癌组织样本中的表达;RT-qpCR和Western blot检测ST6GAL2在结直肠癌细胞系中的表达水平。利用慢病毒感染SW480和HT29细胞,构建ST6GAL2敲降和过表达的稳定细胞系。通过CCK-8增殖实验、克隆形成实验、细胞划痕实验和Transwell侵袭实验分别检测ST6GAL2对细胞增殖、迁移及侵袭能力的影响。结果在TCGA和GEO数据库观察到ST6GAL2在结直肠癌组织中表达低于正常组织(P=0.032),且ST6GAL2在右半结肠癌中较左半结肠癌表达下调(P<0.0001)。预后分析显示在MSS型结肠癌中,ST6GAL2的表达量与总生存期成正相关(P=0.0209)。免疫组化结果显示ST6GAL2在正常组织高表达,而肿瘤组织中相对低表达(P<0.0001);ST6GAL2在右半结肠癌中的表达明显低于左半(P=0.018)。CCK-8与克隆形成实验结果显示敲低ST6GAL2后结肠癌细胞增殖能力增强(P<0.0001)、克隆形成能力增强(P<0.05)。Transwell实验表明ST6GAL2表达下调能促进结肠癌细胞的迁移(P<0.01)和侵袭(P<0.05)。同样的实验方法结果表明过表达ST6GAL2可抑制细胞的增殖和迁移。结论ST6GAL2在结直肠癌组织中表达降低且在右半结肠癌中较左半低表达。MSS型结肠癌中,ST6GAL2的表达与预后正相关。ST6GAL2表达下调会促进CRC细胞的生长、迁移和侵袭;过表达ST6GAL2可抑制细胞的生长和转移。Objective To investigate the effect of ST6GAL2 on the growth and metastasis of colon cancer cells.Methods The effect of ST6GAL2 on the growth and metastasis of colon cancer cells was studied from the bioinformatics,histology,and cytology levels.The expression of ST6GAL2 in colorectal cancer was analyzed based on the TCGA and GEO databases,and the Kaplan-Meier method was used to evaluate the relationship between ST6GAL2 expression and overall survival.Immunohistochemistry was used to verify the expression of ST6GAL2 in colorectal cancer tissue samples.RT-qpCR and Western blot were used to detect the expression level of ST6GAL2 in colorectal cancer cell lines.SW480 and HT29 cells were infected with lentivirus to construct stable cell lines with ST6GAL2 knockdown and overexpression.The effects of ST6GAL2 on cell proliferation,migration,and invasion were detected by CCK-8 assay,colony formation assay,cell scratch assay,and Transwell invasion assay.Results Based on the TCGA and GEO databases,the expression of ST6GAL2 in colorectal cancer tissues was lower than that in normal tissues(P=0.032),and the expression of ST6GAL2 in right-sided colon cancer was lower than that in leftsided colon cancer(P<0.0001).Prognostic analysis showed that the expression of ST6GAL2 was positively correlated with overall survival in MSS-type colon cancer(P=0.0209).Immunohistochemistry results showed that ST6GAL2 was highly expressed in normal tissues but relatively low in tumor tissues(P<0.0001);the expression of ST6GAL2 in right-sided colon cancer was significantly lower than that in left-sided colon cancer(P=0.018).CCK-8 and colony formation assays showed that the proliferation ability(P<0.0001)and colony formation ability(P<0.05)of colon cancer cells were enhanced after ST6GAL2 knockdown.Transwell assay showed that down-regulation of ST6GAL2 expression promoted the migration(P<0.01)and invasion(P<0.05)of colon cancer cells.The results of the same experimental methods showed that overexpression of ST6GAL2 inhibited cell proliferation and

关 键 词：结直肠癌 左/右半结肠癌 ST6GAL2 预后 

分 类 号：R735.3[医药卫生—肿瘤]