环状RNA-PCAC1促进胰腺导管腺癌侵袭转移的研究

Circular RNA-PCAC1 promotes the metastasis of pancreatic ductal adenocarcinoma

目的探讨环状RNA(circRNA)-PCAC1在胰腺导管腺癌中的表达水平及其与患者临床病理特征、预后的关系。方法鉴定circRNA-PCAC1,并通过功能实验观察其对胰腺导管腺癌侵袭转移能力的影响。采用RT-PCR检测76例胰腺导管腺癌组织与配对癌旁组织的circRNA-PCAC1表达水平,Cox回归模型和Kaplan-Meier曲线法分析circRNA-PCAC1与患者临床病理特征和预后的关系。结果功能实验证实circRNA-PCAC1过表达显著促进胰腺导管腺癌侵袭转移能力。胰腺导管腺癌组织中circRNA-PCAC1的表达水平显著高于癌旁组织(P<0.01)。circRNA-PCAC1过表达与胰腺导管腺癌患者不良预后相关(P<0.05)。circRNA-PCAC1是胰腺导管腺癌患者总生存期(HR=1.733,95% CI:1.066~2.991,P=0.030)和无病生存期(HR=1.636,95% CI:1.090~2.811,P=0.042)的独立影响因素。结论 circRNA-PCAC1在胰腺导管腺癌中高表达并促进胰腺导管腺癌侵袭转移,提示其可能成为胰腺导管腺癌临床治疗的新靶点。

Objective To determine the expression of circular RNA (circRNA) and evaluate the value of circRNA for clinicopathologic and prognostic of pancreatic ductal adenocarcinoma.Methods The construction of circRNA-PCAC1 was determined by RT-PCR using random primer or oligo-dT primer.The invasion of pancreatic ductal adenocarcinoma cells were measured by transwell assay in vitro.The expression of circRNA-PCAC1 in a cohort of 76 cases of pancreatic ductal adenocarcinoma tissues and paired normal adjacent tissues were detected by RT-PCR.The clinicopathologic information was collected and analyzed for the correlation with circRNA-PCAC1 expression by using Cox regression model and Kaplan-Meier curve analysis.Results circRNA-PCAC1 promoted pancreatic ductal adenocarcinoma cells invasion.The expression of circRNA-PCAC1 was up-regulated in pancreatic ductal adenocarcinoma compared with normal adjacent tissues (P<0.01).High expression of circRNA-PCAC1 was associated with poor prognosis in pancreatic ductal adenocarcinoma (P<0.05).circRNA-PCAC1 was an independent poor prognostic predictor related to overall survival (HR=1.733,95% CI:1.066-2.991,P=0.030) and disease free survival (HR=1.636,95% CI:1.090-2.811,P=0.042) rate of pancreatic patients.Conclusion circRNA-PAPC1 is up-regulated in pancreatic ductal adenocarcinoma and promotes the invasion and metastasis of pancreatic ductal adenocarcinoma,supporting that circRNA-PCAC1 may be a potential therapeutic target for pancreatic ductal adenocarcinoma.