人胰腺导管腺癌 K-ras 癌基因突变转基因大鼠血清中循环 microRNAs。

Circulating microRNAs in serum of human K-ras oncogene transgenic rats with pancreatic ductal adenocarcinomas.

机构信息

Toxicology Group, Environmental Health Science Laboratory, Sumitomo Chemical Co, Ltd, Osaka, Japan.

出版信息

Pancreas. 2012 Oct;41(7):1013-8. doi: 10.1097/MPA.0b013e31824ac3a5.

DOI:10.1097/MPA.0b013e31824ac3a5

PMID:22513294

Abstract

OBJECTIVES

Novel biomarkers for pancreatic ductal adenocarcinoma (PDAC) are urgently needed because of its poor prognosis. We have previously established an animal model for human PDAC using transgenic rats in which expression of a human K-ras(G12V) oncogene is regulated by the Cre/lox system. Using this model, we searched for candidate circulating microRNAs (miRNAs) for use as novel clinical diagnostic biomarkers for PDAC.

METHODS

Rats bearing PDACs were generated using our model. MicroRNA expression in serum and pancreatic tissues of PDAC and control rats was compared by microarray analysis. Rat serum levels of 28 miRNAs identified by microarray analysis and 4 miRNAs previously reported to be high in plasma of PDAC patients were quantified by real-time quantitative reverse transcription polymerase chain reaction.

RESULTS

Quantification by real-time quantitative polymerase chain reaction revealed that miR-155, miR-21, and miR-210 were higher in serum of PDAC rats, similar to plasma of patients with PDAC. In addition, miR-18a, miR-203, miR-30b-5p, miR-31, miR-369-5p, miR-376a, and miR-541 were higher and miR-375 was lower in the serum of PDAC rats.

CONCLUSION

We identified 4 previously unreported miRNAs (miRNA-203, miRNA-369-5p, miRNA-376a, and miRNA-375) whose expression is significantly different in PDAC rats compared to control rats. These miRNAs need to be quantitated in humans as potential novel clinical diagnostic biomarkers for PDAC.

摘要

目的

由于胰腺导管腺癌 (PDAC) 预后较差，因此迫切需要新的生物标志物。我们之前使用 Cre/lox 系统调控人 K-ras(G12V) 癌基因表达的转基因大鼠建立了 PDAC 动物模型。使用该模型，我们寻找了可作为 PDAC 新型临床诊断生物标志物的候选循环 microRNAs (miRNAs)。

方法

使用我们的模型生成了携带 PDAC 的大鼠。通过微阵列分析比较了 PDAC 和对照大鼠血清和胰腺组织中的 microRNA 表达。通过实时定量逆转录聚合酶链反应定量了 microarray 分析鉴定的 28 种 miRNA 和 4 种先前报道在 PDAC 患者血浆中含量高的 miRNA 在大鼠血清中的水平。

结果

实时定量聚合酶链反应的定量显示，miR-155、miR-21 和 miR-210 在 PDAC 大鼠血清中升高，与 PDAC 患者的血浆相似。此外，miR-18a、miR-203、miR-30b-5p、miR-31、miR-369-5p、miR-376a 和 miR-541 在 PDAC 大鼠血清中升高，miR-375 降低。