Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Surgery. 2011 Nov;150(5):916-22. doi: 10.1016/j.surg.2011.06.017.
MicroRNAs (miRNAs) have been gaining attention as new, key molecules that contribute to carcinogenesis. In pancreatic cancer, previous profiling analyses of miRNA expression have shown that several miRNAs are differently expressed in normal and cancerous tissues. Several pancreatic cancer-specific miRNAs differed, however, in each analysis.
We investigated the miRNA expression profiles of the pancreatic cancer cell lines CAPAN-1 and CFPAC1 and an immortalized human normal pancreatic ductal epithelial cell line (HPDE) using a high-throughput, TaqMan, qRT-PCR array analysis. We also analyzed the expression levels of this miRNA in microdissected (n = 15) and formalin-fixed, paraffin-embedded (FFPE) (n = 115) samples from pancreatic cancers by quantitative RT-PCR. Finally, we investigated the effects of this miRNA on the invasiveness of pancreatic cancer cells.
Based on the microarray analysis, miR-372, miR-146a, miR-204, miR-10a, and miR-10b showed particularly large differences (>10-fold changes) between both pancreatic cell lines and HPDE cells. Thirteen of the 15 pancreatic cancer cell lines showed 2.1- to 36.4-fold (median, 15.3-fold) greater levels of miR-10b than HPDE cells. Microdissection analysis revealed that miR-10b exhibited greater expression levels in pancreatic cancer cells (n = 5) than in normal pancreatic ductal cells (n = 10) (P < .020). Analysis of FFPE samples showed that high miR-10b expression was associated with a lesser overall survival (P = .014). Furthermore, miR-10b correlated with the invasiveness of pancreatic cancer cells (P < .01).
miR-10b is overexpressed in pancreatic cancer and may be involved in the invasiveness in pancreatic cancer cells, thereby leading to a poor prognosis.
微小 RNA(miRNA)作为新的关键分子在癌症发生中发挥作用,引起了人们的关注。在胰腺癌中,miRNA 表达谱的先前分析表明,几种 miRNA 在正常组织和癌组织中的表达不同。然而,在每个分析中,几种胰腺癌特异性 miRNA 都存在差异。
我们使用高通量 TaqMan qRT-PCR 阵列分析研究了胰腺癌细胞系 CAPAN-1 和 CFPAC1 以及永生化人正常胰腺导管上皮细胞系(HPDE)的 miRNA 表达谱。我们还通过定量 RT-PCR 分析了微切割(n = 15)和福尔马林固定、石蜡包埋(FFPE)(n = 115)样本中这种 miRNA 的表达水平。最后,我们研究了这种 miRNA 对胰腺癌细胞侵袭性的影响。
基于微阵列分析,miR-372、miR-146a、miR-204、miR-10a 和 miR-10b 在两种胰腺细胞系和 HPDE 细胞之间表现出特别大的差异(> 10 倍变化)。在 15 种胰腺癌细胞系中,有 13 种细胞系中 miR-10b 的水平比 HPDE 细胞高 2.1 到 36.4 倍(中位数为 15.3 倍)。微切割分析显示,miR-10b 在胰腺癌细胞(n = 5)中的表达水平高于正常胰腺导管细胞(n = 10)(P <.020)。FFPE 样本分析表明,miR-10b 高表达与总体生存率降低相关(P =.014)。此外,miR-10b 与胰腺癌细胞的侵袭性相关(P <.01)。
miR-10b 在胰腺癌中过度表达,可能参与胰腺癌细胞的侵袭性,从而导致预后不良。