高迁移率族蛋白A2促进胃癌细胞侵袭转移及其可能机制

Promotive effect and possible mechanism of high-mobility group protein A2 on invasion and metastasis of gastric cancer cells

目的观察高迁移率族蛋白A2(high-mobility group protein A2,HMGA2)在胃癌组织中的表达及与临床病理特征和预后的关系,探讨HMGA2调控胃癌细胞侵袭和增殖的作用及机制。方法利用TCGA数据库、GTEx数据库及生物信息学分析工具(GEPIA、KM plotter)对HMGA2 mRNA在胃癌中的表达及患者生存时间进行分析。并利用免疫组化检测HMGA2蛋白在胃癌及癌旁组织的表达,分析HMGA2表达与胃癌临床病理学参数的相关性及对预后的影响。在MGC-803细胞中敲低HMGA2,在SGC-7901细胞中过表达HMGA2,并利用平板克隆实验、transwell实验分别检测细胞增殖、侵袭能力的变化。在过表达HMGA2的细胞中敲低Snail1,检测细胞侵袭能力变化,Western Blot检测细胞中HMGA2及EMT标志物的表达变化。结果生物信息学分析发现胃癌组织中HMGA2 mRNA表达相较于正常胃组织显著增加(P<0.05)。免疫组化显示,与癌旁组织相比,胃癌组织中HMGA2蛋白表达量显著升高,且与TNM分期、淋巴结转移以及生存率等相关。HMGA2高表达的胃癌患者,总生存期及无复发生存期明显缩短(P<0.05)。敲低HMGA2后,MGC-803细胞的增殖和侵袭能力降低(P<0.05);过表达HMGA2后SGC-7901细胞的增殖和侵袭能力升高(P<0.05)。在过表达HMGA2的SGC-7901细胞中,敲低Snail1表达,细胞侵袭能力明显降低(P<0.05),且E-cadherin的表达升高,N-cadherin和Vimentin的表达降低。结论HMGA2高表达与胃癌患者的不良预后相关,其可能通过调控Snail1促进胃癌细胞侵袭转移。

Objective To detect the expression of high-mobility group protein A2(HMGA2)in gastric cancer tissues,investigate its relationship with clinicopathological features and prognosis,and explore its role and underlying mechanism in regulating the invasion and proliferation of gastric cancer cells.Methods TCGA database,GTEx database and bioinformatics analysis tools(GEPIA,KM plotter)were used to analyze the expression of HMGA2 gene in gastric cancer and the survival time of patients.The expression of HMGA2 protein in gastric cancer and adjacent tissues was detected by immunohistochemistry,and the correlation between HMGA2 expression and the clinicopathological parameters and its effect on prognosis of gastric cancer patients were analyzed.After HMGA2 was knocked down in gastric cancer cell line MGC-803,and overexpressed in gastric cancer cell line SGC-7901,plate cloning and transwell assay were used to detect the proliferation and invasion ability,respectively.The invasion ability was detected again in the HMGA2 overexpressed SGC-7901 cells after knockdown of Snail1.Western blotting was employed to measure the expression changes of HMGA2 and epithelial to mesenchymal transition(EMT)markers in the cells.Results The bioinformatics analysis showed that the mRNA expression of HMGA2 was significantly increased in gastric cancer tissues compared with normal gastric tissues(P<0.05).Immunohistochemistry also indicated that the protein level of HMGA2 was obviously higher in gastric cancer tissues than para-cancer tissues,and it was associated with TNM staging,lymph node metastasis and survival rate.The gastric cancer patients with high HMGA2 expression had statistically shorter total survival and relapse-free survival(P<0.05).Knockdown of HMGA2 resulted in decreased proliferation and invasion ability in MGC-803 cells decreased(P<0.05),while its overexpression led to enhanced proliferation and invasion ability in SGC-7901 cells(P<0.05).However,knocking down Snail1 would cause the invasion of HMGA2-overexpressed SGC-7901 cells reduced(P<0.05),and the expression level of E-cadherin up-regulated and those of N-cadherin and Vimentin downregulated.Conclusion High HMGA2 expression is associated with poor prognosis of gastric cancer patients,and it may promote invasion and metastasis of gastric cancer cells by regulating Snail1.