MicroRNA-141靶向致癌基因Bmi-1抑制胰腺癌细胞的增殖

MicroRNA-141 suppresses proliferation in pancreatic cancer by targeting oncogene Bmi-1

目的:探讨mi R-141调控胰腺癌细胞增殖的机制。方法:采用q RT-PCR检测正常胰腺细胞和4种胰腺癌细胞株中mi R-141的表达。从Gene Expression Omnibus数据库(GEO)下载包含36例胰腺癌样本和16例正常样本的GSE71533 mi R-141表达文件,分析mi R-141在胰腺癌及癌旁的表达差异。Western blot检测Bmi-1在正常胰腺细胞和4种胰腺癌细胞株中的表达。荧光素酶报告基因检测mi R-141和Bm-1之间的靶向关系。通过CCK8、平板克隆形成检测Bmi-1和mi R-141对胰腺癌细胞增殖能力的影响。结果:q RT-PCR显示与正常胰腺细胞相比,mi R-141在胰腺癌细胞中表达下调;GSE71533数据集分析结果也显示mi R-141在胰腺癌组织中下调;Western blot分析结果表明Bmi-1在胰腺癌细胞中高表达,双荧光素酶实验表明mi R-141锚定在Bmi-1的3′非编码区,下调Bmi-1可以抑制胰腺癌细胞的增殖;上调mi R-141可以降低Bmi-1的蛋白质表达水平,从而抑制胰腺癌细胞中细胞增殖。结论:mi R-141通过靶向Bmi-1在胰腺癌中起抑制作用,在胰腺癌诊疗中具有潜在功能。

Objective：To investigate the mechanism of mi R-141 regulating cell proliferation in pancreatic cancer. Methods：Expression of mi R-141 in normal pancreas cell and four pancreatic cancer cell lines were detected by quantitative reverse transcription PCR（q RT-PCR）. mi R-141 expression file of GSE71533 which including 36 pancreatic cancer samples and 16 normal samples was downloaded from Gene Expression Omnibus（GEO）to analyze the expression of mi R-141. Western blot was used to detect the expression of Bmi-1 in normal pancreatic cell and four pancreatic cancer cells Luciferase reporter assay was performed to analyze the relationship between Bmi-1 and mi R-141. The effects of mi R-141 and Bmi-1 on cell proliferation was examined by CCK8 and colony formation assay,respectively. Results：The q RT-PCR results showed that mi R-141 was significantly down-regulated in pancreatic cancer cells. mi R-141 was down-regulated in pancreatic cancer tissues by analyzing the microarray of GSE71533. Western blot analysis results demonstrated that Bmi-1 was up-regulated in pancreatic cancer cells. The dual luciferase assay indicated that mi R-141 was anchored at the 3′-untranslated region of Bmi-1. Down-regulation of Bmi-1 inhibited the proliferation of pancreatic cancer cells.Upregulating mi R-141 decreased the protein level of Bmi-1,thus repressing cell proliferation in pancreatic cancer cell. Conclusions：mi R-141 acts as a tumor-suppressor in pancreatic cancer by targeting Bmi-1. These findings revealed that mi R-141＇s potential function in the treatment of pancreatic cancer.