MicroRNA-10b is overexpressed in pancreatic cancer, promotes its invasiveness, and correlates with a poor prognosis
MicroRNA-10b is overexpressed in pancreatic cancer, promotes its invasiveness, and correlates with a poor prognosis
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DOI：
10.1016/j.surg.2011.06.017
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发表时间：
2011-11-01
期刊：
影响因子：
3.8
通讯作者：
Tanaka, Masao
中科院分区：
文献类型：
--
作者：
Nakata, Kohei;Ohuchida, Kenoki;Tanaka, Masao
背景microRNAs（miRNAs）作为一种新的、与肿瘤发生有关的关键分子，已引起人们的广泛关注。胰腺癌;先前的miRNA表达谱分析已经表明，几种miRNA在正常和癌组织中表达不同。然而，在每次分析中，几种胰腺癌特异性miRNA不同。我们研究了胰腺癌细胞系CAPAN-1和CFPAC 1和永生化的人正常胰腺导管上皮细胞系（HPDE）的miRNA表达谱使用高通量，TaqMan，qRT-PCR阵列分析。我们还通过定量RT-PCR分析了胰腺癌显微切割（n = 15）和福尔马林固定石蜡包埋（FFPE）（n = 115）样本中该miRNA的表达水平。最后，我们研究了该miRNA对胰腺癌细胞侵袭力的影响。基于微阵列分析，miR-372、miR-146 a、miR-204、miR-10a和miR-10 b在胰腺细胞系和HPDE细胞之间显示出特别大的差异（>10倍变化）。15个胰腺癌细胞系中的13个显示出比HPDE细胞高2.1至36.4倍（中位数，15.3倍）的miR-10 b水平。显微切割分析显示miR-10 b在胰腺癌细胞中的表达水平（n =）高于正常胰腺导管细胞（n = 10）（P <0.020）。FFPE样本的分析显示，高ntiR-10 b表达与较低的总生存率相关（P = 0.014）。miR-10 b与胰腺癌细胞的侵袭性相关（P <0.01）。miR-10 b在胰腺癌中过表达，可能参与胰腺癌细胞的侵袭性，从而导致预后不良。（Surgery 2011;150：916-22.）
Background. 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.Methods. 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.Results. 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 =) than in normal pancreatic ductal cells (n = 10) (P < .020). Analysis of FFPE samples showed that high ntiR-10b expression was associated with a lesser overall survival (P = .014). Furthermore, miR-10b correlated with the invasiveness of pancreatic cancer cells (P < .01).Conclusion. miR-10b is overexpressed in pancreatic cancer and may be involved in the invasiveness in pancreatic cancer cells, thereby leading to a poor prognosis. (Surgery 2011;150:916-22.)