circRNA-CHD2通过miR-30e-3p/MDM2/TP53轴促进胰腺癌侵袭转移  

circRNA-CHD2 promoting metastasis of pancreatic cancer via miR-30e-3p/MDM2/TP53 axis

作　　者：高博文 罗宇明 孔瑶 张丁文 堐益垚 杨家彬 贺兴 李文滨[1] Gao Bowen;Luo Yuming;Kong Yao;Zhang Dingwen;Ya Yiyao;Yang Jiabin;He Xing;Li Wenbin(Department of Biliary and Pancreatic Surgery,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China;Department of General Surgery,Guangdong Provincial People’s Hospital,Guangzhou 510080,China)

机构地区：[1]中山大学孙逸仙纪念医院胆胰外科,广州510120 [2]广东省人民医院普外科,广州510080

出　　处：《中华普通外科学文献（电子版）》2022年第1期14-19,共6页Chinese Archives of General Surgery(Electronic Edition)

基　　金：国家自然科学基金资助项目(81971463)。

摘　　要：目的探究circRNA-CHD2促进胰腺癌侵袭转移的机制。方法采用Kaplan-Meier曲线分析circRNA-CHD2的表达与胰腺癌患者临床病理特征及预后的相关性。通过划痕实验和Transwell实验分析circRNA-CHD2对胰腺癌细胞系侵袭转移功能的影响。采用生物信息学分析、RNA pull-down实验和qPCR实验证明circRNA-CHD2与miR-30e-3p的结合。结果与癌旁组织相比,circRNA-CHD2在胰腺癌组织中的表达显著升高(P<0.01)。circRNA-CHD2的高表达与胰腺癌患者的不良预后相关。体外功能实验表明,circRNA-CHD2的过表达可以促进胰腺癌的侵袭转移。进一步的机制实验提示,circRNA-CHD2能够竞争性结合miRNA-30e-3p,上调靶基因MDM2的表达,进一步抑制TP53的表达。结论 circRNA-CHD2介导miR-30e-3p/MDM2/TP53轴调控胰腺癌的侵袭转移,其有望成为胰腺癌的生物学标志物和治疗靶点。Objective To reveal the mechanisms of circRNA-CHD2 promoting the metastasis of pancreatic cancer.Methods Kaplan-Meier curve was used to analyze the correlation between the expression of circRNA-CHD2 and the clinicopathological characteristics and prognosis of pancreatic cancer.The effect of circRNA-CHD2 on invasion and metastasis of pancreatic cancer cell line was analyzed by scratch test and Transwell test.Bioinformatics analysis,RNA pull-down assay and qPCR method were used to confirm the binding of circRNA-CHD2 and miR-30e-3p.Results There was a significantup-regulation of circRNA-CHD2 in pancreatic cancer tissues compared to tumor-adjacent tissues (P<0.01).Up-regulation of circRNA-CHD2 was correlated with poor prognosis of patients with pancreatic cancer.Functional tests showed that circRNA-CHD2 could promote pancreatic cancer cell metastasis in vitro.Mechanistically,circRNA-CHD2 functioned as a miR-30e-3p endogenous sponge and targetedmiR-30e-3p/MDM2/TP53 axis.Conclusions circRNA-CHD2 can promote metastasis of pancreatic cancer by regulating miR-30e-3p/MDM2/TP53 axis.Therefore,circRNA-CHD2 may serve as a prognostic biomarker and therapeutic target in pancreatic cancer.

关 键 词：胰腺肿瘤 circRNA circRNA-CHD2 miR-30e-3p MDM2 

分 类 号：R735.9[医药卫生—肿瘤]