COL8A1通过竞争性结合miR-876调控SUZ12的表达从而促进胃癌细胞增殖  

COL8A1 promotes proliferation of gastric cancer cells by competitively binding miR-876 to regulate SUZ12 expression

作　　者：屈振杰[1] 崔琴[2] QU Zhenjie;CUI Qin(Department of Oncology,Baogang Hospital,Baotou 014010,China;Department of Gastroenterology,Baogang Hospital,Baotou 014010,China)

机构地区：[1]内蒙古包钢医院肿瘤内科,内蒙古包头014010 [2]内蒙古包钢医院消化内科,内蒙古包头014010

出　　处：《胃肠病学和肝病学杂志》2021年第5期571-577,共7页Chinese Journal of Gastroenterology and Hepatology

摘　　要：目的筛选胃癌中具有显著临床意义的潜在靶基因,探究其在胃癌发生发展中的功能和潜在分子机制。方法通过GEPIA数据库检索对胃癌发生发展具有重要意义的目的基因;采用免疫组化染色法及qRT-PCR检测目的基因在胃癌组织及胃癌前病变组织中的表达;通过siRNA介导敲低目的基因,利用细胞增殖实验和克隆形成实验验证其在胃癌发生发展中的作用;通过生物信息学数据库检测与目的基因结合的microRNA,进一步探索潜在作用机制。结果共筛选出46个基因在胃癌中高表达且具有显著临床预后相关性,最终选择COL8A1作为研究目的基因。胃癌及胃高级别上皮内瘤变组织中COL8A1高于正常组织(P=0.000),与病理T分期显著相关(P<0.05),其高表达患者预后不良。敲低COL8A1表达后,胃癌细胞增殖速率和克隆形成速率显著降低(P<0.05)。过表达miR-876可抑制SUZ12表达,降低细胞增殖速率(P<0.05);同时过表达miR-876和COL8A1可显著上调SUZ12表达(P<0.01),恢复细胞增殖速率至正常水平。结论COL8A1在胃癌中高表达,参与胃癌前病变进展为胃癌的过程,可作为胃癌早期诊断的分子标志物;COL8A1促进胃癌细胞增殖,可能通过竞争性结合miR-876,减弱miR-876与SUZ12结合作用,进而释放SUZ12,促进胃癌的发展。Objective To screen potential target genes with significant clinical significance in gastric cancer and explore their functions and potential molecular mechanisms in the occurrence and development of gastric cancer.Methods High expression of tumor/normal>2 in gastric cancer and genes significantly related to the clinical prognosis of gastric cancer were retrieved by GEPIA database.Target genes with significant clinical significance were identified by coincidence analysis,and the target genes were further screened out by heat map analysis and the principle of poor prognosis of high expression.Immunohistochemical staining and qRT-PCR were used to detect the expression of the target gene in gastric cancer tissues and precancerous tissues.siRNA mediated knockdown of the target gene was used to verify the importance of the target gene in the development of gastric cancer through cell proliferation and cloning experiments.MicroRNA binding with the target gene was detected through bioinformatics database to further explore the potential mechanism of action.Results A total of 46 genes were screened out to be highly expressed in gastric cancer with significant clinical prognostic relevance,and COL8A1 was finally selected as the target gene.Expression of COL8A1 in gastric cancer and high-grade intraepithelial neoplasia tissue was higher than that in normal tissue(P=0.000),which was significantly correlated with pathological T stage(P<0.05).Patients with high expression of COL8A1 had a poor prognosis.After knockdown COL8A1 expression,the proliferation rate and clonal formation rate of gastric cancer cells were significantly decreased(P<0.05).Overexpression of miR-876 inhibited SUZ12 expression and slowed cell proliferation rate(P<0.05);meanwhile,overexpression of miR-876 and COL8A1 significantly upregulated SUZ12 expression(P<0.01)and restored cell proliferation rate to the normal level.Conclusion COL8A1 is highly expressed in gastric cancer and participates in the progression of gastric cancer from precancerous lesions.It

关 键 词：胃癌 COL8A1 miR-876 SUZ12 

分 类 号：R735.2[医药卫生—肿瘤]