LncRNA DNAH17-AS1在胃癌中的表达及意义OA
Expression and clinical implications of lncRNA DNAH17-AS1 in gastric cancer
目的:研究长链非编码 RNA(long non-coding RNA,lncRNA)动力蛋白轴丝重链 17 的反义链 1(dynein axonemal heavy chain 17-antisense strand 1,DNAH17-AS1)在胃癌组织中的表达水平和临床意义,以及对胃癌细胞生物学功能的影响和可能机制.方法:采用实时荧光定量PCR(qRT-PCR)法检测组织标本(108 例胃癌组织及其相应的癌旁组织)、血浆标本(胃癌患者和健康体检者各 25 例)中 lncRNA DNAH17-AS1 相对表达;分析 lncRNA DNAH17-AS1 表达与胃癌患者临床病理特征的相关性.将胃癌AGS、HGC-27 细胞分别分成si-NC对照组和siRNA敲减组,采用脂质体转染方法,分别转染si-NC和si-DNAH17-AS1,通过细胞计数、平板克隆形成实验及Transwell实验分别检测胃癌AGS、HGC-27 细胞增殖、克隆、迁移及侵袭;采用qRT-PCR和蛋白质印迹法分别检测胃癌细胞中相关基因mRNA和蛋白相对表达水平.结果:与癌旁组织相比,lncRNA DNAH17-AS1 在胃癌组织中相对表达量明显增加(P<0.001);胃癌组织中lncRNA DNAH17-AS1 相对表达量与患者TNM分期及淋巴结转移相关(P<0.05);DNAH17-AS1 高表达组患者 5 年生存率较低表达组明显降低(P<0.05);胃癌患者血浆中lncRNA DNAH17-AS1 相对表达量较健康体检者明显增加(P<0.01);血浆DNAH17-AS1 检测胃癌的ROC曲线下面积为 0.721(P<0.01).与si-NC对照组比较,siRNA敲减组胃癌AGS、HGC-27 细胞增殖、克隆、迁移及侵袭明显降低(P均<0.001),E-cad mRNA和蛋白相对表达明显增加(P<0.01),而N-cad、Slug、Snail、ZEB1、MMP9、β-catenin mRNA和蛋白相对表达明显降低(P<0.05 或P<0.01).结论:LncRNA DNAH17-AS1 在胃癌患者癌组织及血浆中呈高表达,且与患者不良预后相关;降低DNAH17-AS1 表达可抑制胃癌细胞增殖、克隆、侵袭及迁移,其作用机制可能与调控上皮间充质转化相关分子表达有关.
Objective:To investigate the expression levels and clinical significance of long non-coding RNA(lncRNA)dynein axonemal heavy chain 17-antisense strand 1(DNAH17-AS1)in gastric cancer tissues,as well as its effect on the biological function of gastric cancer cells and its possible mechanisms.Methods:Real-time quantitative fluorescent PCR(qRT-PCR)was used to detect the expression levels of lncRNA DNAH17-AS1 in tissue samples(108 gastric cancer tissues and corresponding adjacent tissues)and plasma samples(25 gastric cancer patients and 25 healthy people,respectively).Statistical analysis was carried out to analyze the correlation between the expression of DNAH17-AS1 and clinicopathological features of patients with gastric cancer.Gastric cancer AGS and HGC-27 cells were divided into si-NC control group and siRNA knockout group,respectively,and transfected with si-NC and si-DNAH17-AS1 by liposome transfection method.The proliferation,cloning,migration and invasion of AGS and HGC-27 cells were detected by cell counting,plate cloning assay and Transwell assay,respectively.mRNA and protein expression levels of related genes in gastric cancer cells were detected by qRT-PCR and Western blotting,respectively.Results:Compared with adjacent tissues,the relative expression level of lncRNA DNAH17-AS1 in gastric cancer tissues was significantly increased(P<0.001).The relative expression of lncRNA DNAH17-AS1 in gastric cancer tissues was correlated with TNM stage and lymph node metastasis(P<0.05).The 5-year survival rate of patients with high DNAH17-AS1 expression was significantly lower than that of patients with low DNAH17-AS1 expression(P<0.05).The relative expression level of lncRNA DNAH17-AS1 in plasma of patients with gastric cancer was significantly higher than that of healthy subjects(P<0.01);and the area under the ROC curve of plasma DNAH17-AS1 was 0.721(P<0.01).Compared with the si-NC control group,the proliferation,cloning,migration and invasion of gastric cancer AGS and HGC-27 cells in the siRNA knockout group were significantly decreased(P<0.001);and the relative expression of E-cad mRNA and protein was significantly increased(P<0.01),while the mRNA and protein expression of N-cad,transcription factors Slug,Snail,ZEB1,MMP9,and β-catenin was greatly decreased(P<0.05 or P<0.01).Conclusion:LncRNA DNAH17-AS1 is highly expressed in cancer tissues and plasma of patients with gastric cancer,which is associated with poor prognosis of patients.The decrease of DNAH17-AS1 expression could inhibit the proliferation,clone formation,invasion and migration of gastric cancer cells,which may be related to the regulation of epithelial mesenchymal transformation related molecules expression.
张纯;张文波;蒋鹏程
江苏大学附属人民医院普外科,江苏 镇江 212002江苏大学附属人民医院普外科,江苏 镇江 212002江苏大学附属人民医院普外科,江苏 镇江 212002
临床医学
胃癌长链非编码RNA(lncRNA)DNAH17-AS1上皮间充质转化(EMT)
gastric cancerlong non-coding RNA(lncRNA)DNAH17-AS1epithelial-mesenchymal transition(EMT)
《江苏大学学报(医学版)》 2025 (2)
110-117,8
江苏省基础研究计划自然科学基金面上项目(BK20231250)江苏省卫生健康委科研项目(M2022117,M2022100)
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